Strain Name:

B6.129S4-Krastm4Tyj/J

Stock Number:

008179

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This KrasLSL-G12D strain carries a Lox-Stop-Lox (LSL) termination sequence with the K-rasG12D point mutation. When bred to a strain expressing Cre recombinase under control of various tissue specific promoters, Cre recombination deletes the transcriptional termination sequence and allows the expression of the oncogenic protein. There is a phenotypic similarity to the Intrahepatic Cholangiocarcinoma and Granulosa Cell Tumor syndromes in humans. This strain may be useful in studies of cancer and development.

Description

Strain Information

Former Names B6.129S4-Krastm4Tyj/J    (Changed: 02-APR-08 )
Type Congenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating System+/+ sibling x Heterozygote         (Female x Male)   21-NOV-08
Specieslaboratory mouse
GenerationN11+N1F11 (16-DEC-13)
Generation Definitions
 
Donating InvestigatorDr. Tyler Jacks,   Massachusetts Institute of Technology

Description
This KrasLSL-G12D strain carries a point mutation (G12D) whose expression is blocked by the presence of a loxP-flanked stop codon. Homozygotes die in utero. Cre-mediated recombination can excise the stop codon and permit the oncogenic protein to be expressed. Intranasal infection with an adenovirus encoding Cre results in a very high frequency of lung tumors and permits controlled timing of tumor initiation and tumor multiplicity. This strain may be useful in studies of cancer and development.

When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element and a strain expressing a tetracycline-controlled activator protein in lung epithelial cells (see Stock No. 006234 and 006235 respectively), this mutant mouse strain may be useful in studies of lung development.

When bred to a strain expressing Cre recombinase in the male germ line (see Stock No. 003328, 007252 for example), this mutant mouse strain may be useful in studies of embryonic development.

When bred to a strain expressing interferon inducible Cre recombinase (see Stock No. 003556, 005673 for example), this mutant mouse strain may be useful in studies of Ras and myeloproliferative disease.

When bred to a strain expressing Cre recombinase in mammary gland, skin, and other secretory glands (see Stock No. 003553 for example), this mutant mouse strain may be useful in studies of epithelial hyperplasias.

When bred to a strain expressing Cre recombinase in epiblast derived tissues (see Stock No. 003755 for example), this mutant mouse strain may be useful in studies of Ras and embryonic development.

When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of intrahepatic cholangiocarcinoma.

When bred to a strain expressing Cre recombinase in myeloid cell lineage (see Stock No. 004781 for example), this mutant mouse strain may be useful in studies of lung cancer.

When bred to a strain expressing tamoxifen-inducible Cre recombinase in melanocytes (see Stock No. 012328 for example), this mutant mouse strain may be useful in studies of melanomagenesis.

When bred to a strain expressing Cre recombinase in astrocytes (see Stock No. 012887 for example), this mutant mouse strain may be useful in studies of neurofibroma development.

Development
A targeting vector was designed to place a G12D point mutation in exon 1 of the gene and a loxP-flanked STOP element in intron 1, upstream of the mutation. The STOP element incorporates a PGK-puromycin selection cassette at the 5' end in an opposite directional orientation. An adenoviral strong splice acceptor, typically used in gene trap vectors, is fused upstream of the his3 stuffer fragment to prevent splicing around the stopper (in the case that transcription isn't completely silenced). A mutant splice donor site is on the 3' end and a tetrameric tandem array of SV40 PolyA. The stopper was designed to fit into genomic Sal1 or Xho1 sites. The stop cassette prevents the expression of mutant Kras until it is removed by Cre mediated recombination of the Loxp sites, thus allowing expression of oncogenic Kras. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 for more than 10 generations by the donating laboratory which verified correct orientation by Southern assays involving 5' and 3' external and internal probes.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Krastm4Tyj allele
008180   129S/Sv-Krastm4Tyj/J
019104   B6N.Cg-Krastm4Tyj/CjDswJ
View Strains carrying   Krastm4Tyj     (2 strains)

Strains carrying other alleles of Kras
002674   129-Krastm1Tyj/J
008185   129S/Sv-Krastm3Tyj/J
023590   B6(Cg)-Krastm5Tyj/J
008653   B6;129-Krastm5Tyj/J
View Strains carrying other alleles of Kras     (4 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Lung Cancer
Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.
Endometriosis, Susceptibility to, 1
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Bladder Cancer   (KRAS)
Breast Cancer   (KRAS)
Cardiofaciocutaneous Syndrome 2; CFC2   (KRAS)
Gastric Cancer, Hereditary Diffuse; HDGC   (KRAS)
Noonan Syndrome 3; NS3   (KRAS)
Pancreatic Cancer   (KRAS)
Schimmelpenning-Feuerstein-Mims Syndrome; SFM   (KRAS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Krastm4Tyj/Kras+

        B6.129S4-Krastm4Tyj   (conditional)
  • mortality/aging
  • premature death
    • mutants with an intranasal instillation of an adenovirus expressing Cre recombinase have a median survival of 79 days   (MGI Ref ID J:177379)
  • tumorigenesis
  • increased lung adenocarcinoma incidence
    • mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction   (MGI Ref ID J:177379)
  • increased lung adenoma incidence
    • mutants with an intranasal instillation of an adenovirus expressing Cre recombinase develop noninvasive adenoma and adenocarcinoma over a 6-10 week period, characterized by epithelial cell proliferation without destruction of alveolar walls or stromal reaction   (MGI Ref ID J:177379)

Krastm4Tyj/Krastm4Tyj

        B6.129S4-Krastm4Tyj   (conditional)
  • cellular phenotype
  • increased cell proliferation
    • primary mouse embryonic fibroblast treated with adenoviral-cre exhibit enhanced growth rate compared with wild-type cells   (MGI Ref ID J:187371)

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Krastm4Tyj/Kras+

        involves: 129S4/SvJae
  • tumorigenesis
  • increased lung tumor incidence
    • treatment with adenoviral Cre to induce oncogenic Kras expression results in lung tumor development, but causes a lower tumor burden and decreased overall tumor area compared to induced mutants on a Spry2-null background   (MGI Ref ID J:119477)

Krastm4Tyj/Kras+

        involves: 129S4/SvJae   (conditional)
  • mortality/aging
  • premature death
    • median life span of cre adenovirus-treated mice is 32 weeks   (MGI Ref ID J:147590)
  • tumorigenesis
  • altered tumor morphology
    • tumors from cre adenovirus-treated mice exhibit increased cell proliferation compared to in tumors from Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice   (MGI Ref ID J:147590)
    • decreased tumor growth/size
      • cre adenovirus-treated mice develop smaller tumors than in cre adenovirus-treated Krastm4Tyj/Kras+ Rbl2tm2Tyj/Rbl2tm2Tyj mice   (MGI Ref ID J:147590)
  • increased lung tumor incidence
    • mice treated with adenovirus cre develop lung lesions in 4 to 6 months   (MGI Ref ID J:147590)
    • cre adenovirus-treated mice develop lung adenocarcinomas, papillary adenomas and bronchiolar hyperplasia and dysplasia   (MGI Ref ID J:147590)
    • cre adenovirus-treated mice develop fewer tumors than in Krastm4Tyj/Kras+ Rb1tm3Tyj/Rb1tm3Tyj mice   (MGI Ref ID J:147590)
    • large tumors easily visible on the surface of the lungs at eight weeks after Cre-adenovirus treatment   (MGI Ref ID J:158937)
    • increased lung adenoma incidence
      • presence of atypical adenomatous hyperplasia after Cre-adenovirus treatment   (MGI Ref ID J:158937)
    • increased lung carcinoma incidence
      • the most common lesion is adenocarcinoma after Cre-adenovirus treatment   (MGI Ref ID J:158937)
      • increased lung adenocarcinoma incidence
        • in cre adenovirus-treated mice   (MGI Ref ID J:147590)
  • respiratory system phenotype
  • abnormal bronchiole morphology
    • cre adenovirus-treated mice develop bronchiolar hyperplasia and dysplasia unlike wild-type mice   (MGI Ref ID J:147590)
    • bronchiolar epithelial hyperplasia
      • in cre adenovirus-treated mice   (MGI Ref ID J:147590)
  • lung epithelium hyperplasia
    • presence of epithelial hyperplasia after Cre-adenovirus treatment   (MGI Ref ID J:158937)
  • thick pulmonary interalveolar septum
    • in cre adenovirus-treated mice   (MGI Ref ID J:147590)
  • immune system phenotype
  • increased regulatory T cell number
    • following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice   (MGI Ref ID J:154046)
  • hematopoietic system phenotype
  • increased regulatory T cell number
    • following injection of a cre adenovirus in the ovarian bursa, mice with endometriosis also exhibit an increase in spleen and regional lymph nodes T regulatory cells compared with un-injected Krastm4Tyj Tg(MUC1)79.24Gend mice   (MGI Ref ID J:154046)
  • reproductive system phenotype
  • uterus adenomyosis
    • following injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj micefollowing injection of a cre adenovirus in the ovarian bursa, mice develop ovarian lesions consisting of endometrial glandular epithelium unlike un-injected Krastm4Tyj mice   (MGI Ref ID J:154046)

Krastm4Tyj/Kras+

        either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * C3H/HeJ)   (conditional)
  • endocrine/exocrine gland phenotype
  • abnormal ovary morphology
    • after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection   (MGI Ref ID J:96296)
  • growth/size/body phenotype
  • abnormal peritoneum morphology
    • 47% of mutants develop peritoneal endometriosis following ovarian intrabursal injection of an adenovirus expressing Cre   (MGI Ref ID J:96296)
    • however, mice injected with adenovirus expressing Cre directly into the peritoneum do not develop peritoneal endometriosis   (MGI Ref ID J:96296)
  • reproductive system phenotype
  • abnormal ovary morphology
    • after ovarian intrabursal injection of an adenovirus expressing Cre, mutants develop benign ovarian endometriosis-like lesions, however no invasive ovarian tumors are seen up to 10 months following adenoviral injection   (MGI Ref ID J:96296)

Krastm4Tyj/Kras+

        involves: 129S4/SvJae * C57BL/6   (conditional)
  • tumorigenesis
  • increased lung adenoma incidence
    • lung adenocarcinomas cover 11% of lung area 9 weeks after administration of a Cre-recombinase expressing adenovirus   (MGI Ref ID J:203686)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Krastm4Tyj/Kras+ Lyz2tm1(cre)Ifo/Lyz2+

        involves: 129P2/OlaHsd * 129S4/SvJae   (conditional)
  • mortality/aging
  • complete postnatal lethality
    • the maximum survival is 24 days   (MGI Ref ID J:158937)
  • respiratory system phenotype
  • increased lung weight
    • lung weight is 10-fold higher than that in control mice at 3 weeks old   (MGI Ref ID J:158937)
  • tumorigenesis
  • increased lung tumor incidence   (MGI Ref ID J:158937)

Krastm4Tyj/Kras+ Tg(Alb-cre)21Mgn/0

        involves: 129S4/SvJae * C57BL/6 * DBA   (conditional)
  • tumorigenesis
  • increased cholangiocarcinoma incidence
    • mutants develop invasive intrahepatic cholangiocarcinoma with low penetrance (1 of 8 mutants) and long latency (at 36 weeks of age)   (MGI Ref ID J:184949)

Krastm4Tyj/Kras+ Tg(Gfap-cre)77.6Mvs/0

        involves: 129 * BALB/c * C57BL/6NHsd   (conditional)
  • tumorigenesis
  • *normal* tumorigenesis
    • mutants do not develop tumors   (MGI Ref ID J:154673)

Krastm4Tyj/Kras+ Tg(Krt1-15-cre/PGR)22Cot/0

        involves: 129S4/SvJae * C57BL/6 * SJL   (conditional)
  • tumorigenesis
  • increased facial tumor incidence
    • 2-4 months following RU486 treatment, tumors develop in the face in 35% of treated mutants   (MGI Ref ID J:172048)
    • increased lip tumor incidence
      • 2-4 months following RU486 treatment, lip tumors develop in 57% of treated mice   (MGI Ref ID J:172048)
  • increased skin tumor incidence
    • 2-4 months following RU486 treatment, tumors develop in the back skin in 14% of treated mice   (MGI Ref ID J:172048)
    • increased skin papilloma incidence
      • skin tumors are benign papillomas with no sign of malignant transformtion seen up to 4 months after treatment with RU486   (MGI Ref ID J:172048)
      • double mutants not treated with tamoxifen develop some papillomas but with increased latency (>6 months)   (MGI Ref ID J:172048)
  • integument phenotype
  • increased skin tumor incidence
    • 2-4 months following RU486 treatment, tumors develop in the back skin in 14% of treated mice   (MGI Ref ID J:172048)
    • increased skin papilloma incidence
      • skin tumors are benign papillomas with no sign of malignant transformtion seen up to 4 months after treatment with RU486   (MGI Ref ID J:172048)
      • double mutants not treated with tamoxifen develop some papillomas but with increased latency (>6 months)   (MGI Ref ID J:172048)

Krastm4Tyj/Kras+ Tg(Krt1-15-cre/PGR)22Cot/0

        involves: 129S4/SvJae * C57BL/6 * C57BL/6J * SJL/J   (conditional)
  • tumorigenesis
  • increased papilloma incidence
    • mice develop benign papillomas without progressing to malignancy following topical application of RU486 to the back of skin at 3 weeks of age for 5 days   (MGI Ref ID J:203922)

Krastm4Tyj/Kras+ Tg(MMTV-cre)4Mam/0

        involves: 129S4/SvJae * FVB   (conditional)
  • endocrine/exocrine gland phenotype
  • submandibular gland hyperplasia
    • submandibular gland hyperplasia is seen in mutant mice   (MGI Ref ID J:89333)
  • digestive/alimentary phenotype
  • submandibular gland hyperplasia
    • submandibular gland hyperplasia is seen in mutant mice   (MGI Ref ID J:89333)

Krastm4Tyj/Kras+ Tg(Mx1-cre)1Cgn/?

        involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA   (conditional)
  • mortality/aging
  • premature death
    • survival for around 35 days after pI-pC treatment   (MGI Ref ID J:88163)
    • survival of around 58 days even without pI-pC treatment   (MGI Ref ID J:88163)
  • tumorigenesis
  • increased T cell derived lymphoma incidence
    • thymic T-cell lymphomas   (MGI Ref ID J:88163)
  • increased lung adenoma incidence
    • nodules in lungs   (MGI Ref ID J:88163)
  • increased papilloma incidence
    • squamous papillomas   (MGI Ref ID J:88163)
  • growth/size/body phenotype
  • cachexia
    • becoming emaciated   (MGI Ref ID J:88163)
  • hematopoietic system phenotype
  • abnormal hematopoiesis
    • develop lethal hematopoietic disease   (MGI Ref ID J:88163)
    • abnormal erythrocyte morphology   (MGI Ref ID J:88163)
      • decreased hematocrit
        • average hematocrit of 27%   (MGI Ref ID J:88163)
    • extramedullary hematopoiesis
      • expansion of red pulp in spleen by granulocyte/monocyte lineages in 11 out of 16 cases   (MGI Ref ID J:88163)
      • erythroid expansion was seen in red pulp of spleen in 5 of 16 cases   (MGI Ref ID J:88163)
    • increased leukocyte cell number
      • leukocytosis, usually involving increases in granulocytes   (MGI Ref ID J:88163)
    • myeloid hyperplasia
      • myeloproliferative phenotype   (MGI Ref ID J:88163)
      • myeloid hyperplasia of bone marrow   (MGI Ref ID J:88163)
  • immune system phenotype
  • increased leukocyte cell number
    • leukocytosis, usually involving increases in granulocytes   (MGI Ref ID J:88163)
  • myeloid hyperplasia
    • myeloproliferative phenotype   (MGI Ref ID J:88163)
    • myeloid hyperplasia of bone marrow   (MGI Ref ID J:88163)
  • liver/biliary system phenotype
  • abnormal hepatobiliary system morphology
    • perivascular and periportal infiltration in liver by myeloid and erythroid cells similar to what is seen in spleen   (MGI Ref ID J:88163)
  • integument phenotype
  • ruffled hair
    • ruffled fur   (MGI Ref ID J:88163)

Krastm4Tyj/Kras+ Tg(Tyr-cre/ERT2)13Bos/0

        involves: 129S4/SvJae * FVB   (conditional)
  • tumorigenesis
  • increased melanoma incidence
    • 1 in 14 tamoxifen treated mice develops melanoma with a median tumor latency greater than 52 weeks   (MGI Ref ID J:164588)
  • pigmentation phenotype
  • abnormal melanocyte morphology
    • tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice   (MGI Ref ID J:164588)
  • hyperpigmentation
    • tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice   (MGI Ref ID J:164588)

Krastm4Tyj/Krastm4Tyj Tg(Prm-cre)58Og/0

        involves: 129S4/SvJae   (conditional)
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • mutants die between E9.5 and 11.5   (MGI Ref ID J:119477)
  • embryogenesis phenotype
  • abnormal placenta labyrinth morphology
    • marked defect in inner labyrinth layer is observed at E9.5   (MGI Ref ID J:119477)
    • abnormal placental labyrinth vasculature morphology
      • fetal blood vessels underlying inner labyrinth layer are absent   (MGI Ref ID J:119477)
  • absent vitelline blood vessels
    • at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent   (MGI Ref ID J:119477)
  • embryonic growth arrest
    • embryos show developmental arrest   (MGI Ref ID J:119477)
  • pale yolk sac
    • at E9.5, yolk sacs are pale and roughened   (MGI Ref ID J:119477)
  • cellular phenotype
  • increased apoptosis
    • at death, embryos exhibit widespread apoptosis   (MGI Ref ID J:119477)
  • cardiovascular system phenotype
  • abnormal placental labyrinth vasculature morphology
    • fetal blood vessels underlying inner labyrinth layer are absent   (MGI Ref ID J:119477)
  • absent vitelline blood vessels
    • at E9.5 vasculature is poorly developed; vasculature has a primitive honeycomb-like network lacking branching vitelline vessels, while large vitelline vessels are absent   (MGI Ref ID J:119477)

Krastm4Tyj/Krastm4Tyj Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0

        involves: 129/Sv * C57BL/6   (conditional)
  • mortality/aging
  • complete postnatal lethality
    • death in the early postnatal period   (MGI Ref ID J:119477)
  • respiratory system phenotype
  • abnormal branching involved in lung morphogenesis
    • with doxycycline treatment beginning at E6.5, a dramatic lung branching defect is observed   (MGI Ref ID J:119477)
    • at E16.5, lungs show even more severe defects than in Kras:Meox2-cre embryos, with large epithelial-lined pouches in place of finely branched network of airways seen in wild-type   (MGI Ref ID J:119477)
    • branching defect persists through late gestation leading to early postnatal lethality   (MGI Ref ID J:119477)
  • abnormal lung epithelium morphology
    • branching defect originates in epithelium rather than mesenchyme   (MGI Ref ID J:119477)
    • abnormal bronchus epithelium morphology
      • markers of ciliated and Clara cells in the bronchi are significantly reduced at E18.5 compared to controls, indicating block in differentiation of lung epithelium   (MGI Ref ID J:119477)

Krastm4Tyj/Krastm4Tyj Tg(Tek-cre)12Flv/0

        involves: 129S4/SvJae * C3H * C57BL/6   (conditional)
  • embryogenesis phenotype
  • *normal* embryogenesis phenotype
    • mutants show normal vascularization of the yolk sac and placental labyrinth   (MGI Ref ID J:119477)

Krastm4Tyj/Kras+ Meox2tm1(cre)Sor/Meox2+

        involves: 129S4/SvJae * 129S4/SvJaeSor   (conditional)
  • mortality/aging
  • complete lethality throughout fetal growth and development
    • homozygous embryos die by E14.5   (MGI Ref ID J:119477)
  • partial embryonic lethality during organogenesis
    • embryos are recovered at a lower frequency (15% vs expected 25%) at E13.5   (MGI Ref ID J:119477)
  • embryogenesis phenotype
  • *normal* embryogenesis phenotype
    • mutants show normal vascularization of the yolk sac and placental labyrinth   (MGI Ref ID J:119477)
    • abnormal embryonic erythropoiesis
      • fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls   (MGI Ref ID J:119477)
      • abnormal embryonic erythrocyte morphology
        • red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation   (MGI Ref ID J:119477)
  • cardiovascular system phenotype
  • abnormal atrioventricular valve morphology
    • atrioventricular valve malformations   (MGI Ref ID J:119477)
  • abnormal cardiovascular system physiology
    • heart defects lead to heart failure and death in embryos by ~E14.5   (MGI Ref ID J:119477)
    • hemorrhage
      • embryos appear normal at E12.5, but rapidly develop peripheral hemorrhages by E13.5, consistent with heart failure   (MGI Ref ID J:119477)
  • conotruncal ridge hyperplasia
    • excess cushion tissue often leads to obstructed outflow tract   (MGI Ref ID J:119477)
  • double outlet right ventricle
    • at E13.5, embryos frequently show double outlet right ventricle   (MGI Ref ID J:119477)
  • ventricular septal defect
    • all embryonic hearts have prominent septal defects   (MGI Ref ID J:119477)
  • hematopoietic system phenotype
  • abnormal embryonic erythropoiesis
    • fetal-derived hematopoietic progenitors form larger CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) colonies compared with controls   (MGI Ref ID J:119477)
    • abnormal embryonic erythrocyte morphology
      • red blood cells appear immature compared to wild-type and occasionally highly atypical, consisten with a block in erythroid differentiation   (MGI Ref ID J:119477)
  • respiratory system phenotype
  • abnormal branching involved in lung morphogenesis
    • defects in lung branching are apparent by E11.5 compared to controls in vivo and in cultured lungs   (MGI Ref ID J:119477)
    • decrease in branching is associated with formation of large, fluid-filled sacs rather than normal terminal branches   (MGI Ref ID J:119477)
    • impaired branching involved in bronchus morphogenesis
      • at E12.5, mutant lungs exhibit large dilated bronchi whereas wild-type lungs show secondary and tertiary bronchi   (MGI Ref ID J:119477)
      • at E14.5, mutants lungs display dilated bronchi and only a few terminal bronchi   (MGI Ref ID J:119477)
    • impaired branching involved in terminal bronchiole morphogenesis
      • at E14.5, mutants lungs display only a few terminal bronchioles   (MGI Ref ID J:119477)
  • abnormal bronchus morphology
    • at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5   (MGI Ref ID J:119477)
    • impaired branching involved in bronchus morphogenesis
      • at E12.5, mutant lungs exhibit large dilated bronchi whereas wild-type lungs show secondary and tertiary bronchi   (MGI Ref ID J:119477)
      • at E14.5, mutants lungs display dilated bronchi and only a few terminal bronchi   (MGI Ref ID J:119477)
  • dilated respiratory conducting tubes
    • at E12.5, lungs exhibit large dilated bronchi; defect is more pronounced at E14.5   (MGI Ref ID J:119477)
  • liver/biliary system phenotype
  • increased hepatocyte apoptosis
    • at E12.5 fetal livers show large areas of apoptosis   (MGI Ref ID J:119477)
  • liver hypoplasia
    • at E12.5, fetal livers appear hypocellular   (MGI Ref ID J:119477)
  • homeostasis/metabolism phenotype
  • edema
    • embryos appear normal at E12.5, but rapidly develop edema by E13.5, consistent with heart failure   (MGI Ref ID J:119477)
  • integument phenotype
  • pallor
    • embryos appear normal at E12.5, but rapidly develop pallor by E13.5, consistent with heart failure   (MGI Ref ID J:119477)
  • cellular phenotype
  • increased hepatocyte apoptosis
    • at E12.5 fetal livers show large areas of apoptosis   (MGI Ref ID J:119477)

Krastm4Tyj/Kras+ Shhtm2(cre/ERT2)Cjt/Shh+

        involves: 129S2/SvPas * 129S4/SvJae   (conditional)
  • integument phenotype
  • *normal* integument phenotype
    • no epidermal defects or tumor formation are observed with tamoxifen treatment at day 28 (during period of up to 4 months after cre induction) when hair follicles are in full anlagen   (MGI Ref ID J:172048)
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Research Applications
This mouse can be used to support research in many areas including:

Developmental Biology Research
Embryonic Lethality (Homozygous)

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Krastm4Tyj
Allele Name targeted mutation 4, Tyler Jacks
Allele Type Targeted (Floxed/Frt)
Common Name(s) K-Ras(G12D)fl; K-RasG12D; K-rasLSL; KR; Kras2tm4Tyj; Kras2tm14Tyj; KrasG12D; KrasLSL-G12D; KrasLox; LSL-K-ras G12D; LSL-K-rasG12D; LSL-Kras G12D; LSL-KrasG12D; LSL-KrasG12D; caKRas;
Mutation Made ByDr. Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin129S4/SvJae
ES Cell Line Strain129
Gene Symbol and Name Kras, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
Chromosome 6
Gene Common Name(s) AI929937; C-K-RAS; CFC2; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; K-ras; KI-RAS; KRAS1; KRAS2; Kirsten rat sarcoma oncogene 2, expressed; Kras-2; Kras2; NS; NS3; RASK2; expressed sequence AI929937;
General Note Phenotypic Similarity to Human Syndrome: Intrahepatic Cholangiocarcinoma (J:184949).

Phenotypic Similarity to Human Syndrome: Granulosa cell tumor (GCT) J:186144

Phenotypic Similarity to Human Syndrome: Granulosa cell tumor of the testis (GCTT) J:186144

Phenotypic Similarity to Human Syndrome: Squamous Cell Carcinoma J:203922 in double Kras and Smad4 mutants.

Phenotypic Similarity to Human Syndrome: Soft Tissue Sarcoma J:125101 in double Kras and Trp53 mutants and in double Kras and Cdkn2a mutants.

Phenotypic Similarity to Human Syndrome: Soft Tissue Sarcoma, Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma J:155389, J:204376 in double Kras and Trp53 mutants.

Molecular Note By homologous recombination in ES cells, the Kras2 locus was targeted with a cassette containing an oncogenic form of the KRAS2 protein in which the glycine at position 12 had been substituted with a an aspartic acid. A loxP flanked stop codon was included upstream of the inserted Kras2 sequence, such that the mutant transcript would be expressed only after cre-mediated recombination. [MGI Ref ID J:73445]

Genotyping

Genotyping Information

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Krastm4Tyj,

SEPARATED MELT


Krastm4Tyj, Separated PCR
Krastm4Tyj, Standard PCR


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References

References provided by MGI

Selected Reference(s)

Jackson EL; Willis N; Mercer K; Bronson RT; Crowley D; Montoya R; Jacks T; Tuveson DA. 2001. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15(24):3243-8. [PubMed: 11751630]  [MGI Ref ID J:73445]

Additional References

Krastm4Tyj related

Abel TW; Clark C; Bierie B; Chytil A; Aakre M; Gorska A; Moses HL. 2009. GFAP-Cre-mediated activation of oncogenic K-ras results in expansion of the subventricular zone and infiltrating glioma. Mol Cancer Res 7(5):645-53. [PubMed: 19435821]  [MGI Ref ID J:205246]

Abrigo M; Alvarez R; Paparella ML; Calb DE; Bal de Kier Joffe E; Gutkind JS; Raimondi AR. 2014. Impairing squamous differentiation by Klf4 deletion is sufficient to initiate tongue carcinoma development upon K-Ras activation in mice. Carcinogenesis 35(3):662-9. [PubMed: 24148820]  [MGI Ref ID J:206523]

Acin S; Li Z; Mejia O; Roop DR; El-Naggar AK; Caulin C. 2011. Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer progression in response to oncogenic K-ras. J Pathol 225(4):479-89. [PubMed: 21952947]  [MGI Ref ID J:177463]

Aguirre AJ; Bardeesy N; Sinha M; Lopez L; Tuveson DA; Horner J; Redston MS; DePinho RA. 2003. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 17(24):3112-26. [PubMed: 14681207]  [MGI Ref ID J:87196]

Ahmad I; Singh LB; Foth M; Morris CA; Taketo MM; Wu XR; Leung HY; Sansom OJ; Iwata T. 2011. K-Ras and {beta}-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder. Dis Model Mech 4(4):548-55. [PubMed: 21504907]  [MGI Ref ID J:174242]

Ahn YH; Yang Y; Gibbons DL; Creighton CJ; Yang F; Wistuba II; Lin W; Thilaganathan N; Alvarez CA; Roybal J; Goldsmith EJ; Tournier C; Kurie JM. 2011. Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing peroxisome proliferator-activated receptor gamma2 expression. Mol Cell Biol 31(21):4270-85. [PubMed: 21896780]  [MGI Ref ID J:178325]

Aichler M; Seiler C; Tost M; Siveke J; Mazur PK; Da Silva-Buttkus P; Bartsch DK; Langer P; Chiblak S; Durr A; Hofler H; Kloppel G; Muller-Decker K; Brielmeier M; Esposito I. 2012. Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues. J Pathol 226(5):723-34. [PubMed: 21984419]  [MGI Ref ID J:183335]

Al Saati T; Clerc P; Hanoun N; Peuget S; Lulka H; Gigoux V; Capilla F; Beluchon B; Couvelard A; Selves J; Buscail L; Carrier A; Dusetti N; Dufresne M. 2013. Oxidative stress induced by inactivation of TP53INP1 cooperates with KrasG12D to initiate and promote pancreatic carcinogenesis in the murine pancreas. Am J Pathol 182(6):1996-2004. [PubMed: 23578383]  [MGI Ref ID J:198521]

Andreadi C; Cheung LK; Giblett S; Patel B; Jin H; Mercer K; Kamata T; Lee P; Williams A; McMahon M; Marais R; Pritchard C. 2012. The intermediate-activity L597VBRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway. Genes Dev 26(17):1945-58. [PubMed: 22892241]  [MGI Ref ID J:187371]

Ardito CM; Gruner BM; Takeuchi KK; Lubeseder-Martellato C; Teichmann N; Mazur PK; Delgiorno KE; Carpenter ES; Halbrook CJ; Hall JC; Pal D; Briel T; Herner A; Trajkovic-Arsic M; Sipos B; Liou GY; Storz P; Murray NR; Threadgill DW; Sibilia M; Washington MK; Wilson CL; Schmid RM; Raines EW; Crawford HC; Siveke JT. 2012. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 22(3):304-17. [PubMed: 22975374]  [MGI Ref ID J:190126]

Avila JL; Troutman S; Durham A; Kissil JL. 2012. Notch1 is not required for acinar-to-ductal metaplasia in a model of Kras-induced pancreatic ductal adenocarcinoma. PLoS One 7(12):e52133. [PubMed: 23284900]  [MGI Ref ID J:195622]

Aytes A; Mitrofanova A; Kinkade CW; Lefebvre C; Lei M; Phelan V; Lekaye HC; Koutcher JA; Cardiff RD; Califano A; Shen MM; Abate-Shen C. 2013. ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. Proc Natl Acad Sci U S A 110(37):E3506-15. [PubMed: 23918374]  [MGI Ref ID J:200917]

Badea CT; Athreya KK; Espinosa G; Clark D; Ghafoori AP; Li Y; Kirsch DG; Johnson GA; Annapragada A; Ghaghada KB. 2012. Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent. PLoS One 7(4):e34496. [PubMed: 22485175]  [MGI Ref ID J:187115]

Baek ST; Tallquist MD. 2012. Nf1 limits epicardial derivative expansion by regulating epithelial to mesenchymal transition and proliferation. Development 139(11):2040-9. [PubMed: 22535408]  [MGI Ref ID J:183991]

Bai H; Li H; Zhang W; Matkowskyj KA; Liao J; Srivastava SK; Yang GY. 2011. Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice. Carcinogenesis 32(11):1689-96. [PubMed: 21859833]  [MGI Ref ID J:177398]

Bardeesy N; Aguirre AJ; Chu GC; Cheng KH; Lopez LV; Hezel AF; Feng B; Brennan C; Weissleder R; Mahmood U; Hanahan D; Redston MS; Chin L; Depinho RA. 2006. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci U S A 103(15):5947-52. [PubMed: 16585505]  [MGI Ref ID J:108298]

Bardeesy N; Cheng KH; Berger JH; Chu GC; Pahler J; Olson P; Hezel AF; Horner J; Lauwers GY; Hanahan D; DePinho RA. 2006. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 20(22):3130-46. [PubMed: 17114584]  [MGI Ref ID J:116130]

Basseres DS; Ebbs A; Levantini E; Baldwin AS. 2010. Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis. Cancer Res 70(9):3537-46. [PubMed: 20406971]  [MGI Ref ID J:159456]

Bayne LJ; Beatty GL; Jhala N; Clark CE; Rhim AD; Stanger BZ; Vonderheide RH. 2012. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21(6):822-35. [PubMed: 22698406]  [MGI Ref ID J:189283]

Beilke S; Oswald F; Genze F; Wirth T; Adler G; Wagner M. 2010. The zinc-finger protein KCMF1 is overexpressed during pancreatic cancer development and downregulation of KCMF1 inhibits pancreatic cancer development in mice. Oncogene 29(28):4058-67. [PubMed: 20473331]  [MGI Ref ID J:162125]

Bennecke M; Kriegl L; Bajbouj M; Retzlaff K; Robine S; Jung A; Arkan MC; Kirchner T; Greten FR. 2010. Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell 18(2):135-46. [PubMed: 20708155]  [MGI Ref ID J:163673]

Besmer DM; Curry JM; Roy LD; Tinder TL; Sahraei M; Schettini J; Hwang SI; Lee YY; Gendler SJ; Mukherjee P. 2011. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis. Cancer Res 71(13):4432-42. [PubMed: 21558393]  [MGI Ref ID J:173616]

Blum JM; Ano L; Li Z; Van Mater D; Bennett BD; Sachdeva M; Lagutina I; Zhang M; Mito JK; Dodd LG; Cardona DM; Dodd RD; Williams N; Ma Y; Lepper C; Linardic CM; Mukherjee S; Grosveld GC; Fan CM; Kirsch DG. 2013. Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells. Cell Rep 5(4):933-40. [PubMed: 24239359]  [MGI Ref ID J:205518]

Borczuk AC; Sole M; Lu P; Chen J; Wilgus ML; Friedman RA; Albelda SM; Powell CA. 2011. Progression of Human Bronchioloalveolar Carcinoma to Invasive Adenocarcinoma Is Modeled in a Transgenic Mouse Model of K-ras-Induced Lung Cancer by Loss of the TGF-beta Type II Receptor. Cancer Res 71(21):6665-75. [PubMed: 21911454]  [MGI Ref ID J:177379]

Bornstein S; White R; Malkoski S; Oka M; Han G; Cleaver T; Reh D; Andersen P; Gross N; Olson S; Deng C; Lu SL; Wang XJ. 2009. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation. J Clin Invest 119(11):3408-19. [PubMed: 19841536]  [MGI Ref ID J:154600]

Brady CA; Jiang D; Mello SS; Johnson TM; Jarvis LA; Kozak MM; Kenzelmann Broz D; Basak S; Park EJ; McLaughlin ME; Karnezis AN; Attardi LD. 2011. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145(4):571-83. [PubMed: 21565614]  [MGI Ref ID J:173395]

Braun BS; Archard JA; Van Ziffle JA; Tuveson DA; Jacks TE; Shannon K. 2006. Somatic activation of a conditional KrasG12D allele causes ineffective erythropoiesis in vivo. Blood 108(6):2041-4. [PubMed: 16720837]  [MGI Ref ID J:115071]

Braun BS; Tuveson DA; Kong N; Le DT; Kogan SC; Rozmus J; Le Beau MM; Jacks TE; Shannon KM. 2004. Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 101(2):597-602. [PubMed: 14699048]  [MGI Ref ID J:87429]

Budiu RA; Diaconu I; Chrissluis R; Dricu A; Edwards RP; Vlad AM. 2009. A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells. Dis Model Mech 2(11-12):593-603. [PubMed: 19841240]  [MGI Ref ID J:154046]

Cai H; Memarzadeh S; Stoyanova T; Beharry Z; Kraft AS; Witte ON. 2012. Collaboration of Kras and androgen receptor signaling stimulates EZH2 expression and tumor-propagating cells in prostate cancer. Cancer Res 72(18):4672-81. [PubMed: 22805308]  [MGI Ref ID J:191340]

Cai Z; Feng GS; Zhang X. 2010. Temporal requirement of the protein TyrosinePhosphatase Shp2 in establishing the neuronal fatein early retinal development. J Neurosci 30(11):4110-9. [PubMed: 20237281]  [MGI Ref ID J:159104]

Cai Z; Tao C; Li H; Ladher R; Gotoh N; Feng GS; Wang F; Zhang X. 2013. Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma. Development 140(13):2711-23. [PubMed: 23720040]  [MGI Ref ID J:198655]

Calcagno SR; Li S; Colon M; Kreinest PA; Thompson EA; Fields AP; Murray NR. 2008. Oncogenic K-ras promotes early carcinogenesis in the mouse proximal colon. Int J Cancer 122(11):2462-70. [PubMed: 18271008]  [MGI Ref ID J:135568]

Caldwell ME; DeNicola GM; Martins CP; Jacobetz MA; Maitra A; Hruban RH; Tuveson DA. 2012. Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer. Oncogene 31(12):1599-608. [PubMed: 21860420]  [MGI Ref ID J:186145]

Carretero J; Shimamura T; Rikova K; Jackson AL; Wilkerson MD; Borgman CL; Buttarazzi MS; Sanofsky BA; McNamara KL; Brandstetter KA; Walton ZE; Gu TL; Silva JC; Crosby K; Shapiro GI; Maira SM; Ji H; Castrillon DH; Kim CF; Garcia-Echeverria C; Bardeesy N; Sharpless NE; Hayes ND; Kim WY; Engelman JA; Wong KK. 2010. Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. Cancer Cell 17(6):547-59. [PubMed: 20541700]  [MGI Ref ID J:160885]

Carriere C; Seeley ES; Goetze T; Longnecker DS; Korc M. 2007. The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia. Proc Natl Acad Sci U S A 104(11):4437-42. [PubMed: 17360542]  [MGI Ref ID J:120054]

Carriere C; Young AL; Gunn JR; Longnecker DS; Korc M. 2011. Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the nestin cell lineage. PLoS One 6(11):e27725. [PubMed: 22140463]  [MGI Ref ID J:181133]

Carriere C; Young AL; Gunn JR; Longnecker DS; Korc M. 2009. Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras. Biochem Biophys Res Commun 382(3):561-5. [PubMed: 19292977]  [MGI Ref ID J:147870]

Caulin C; Nguyen T; Lang GA; Goepfert TM; Brinkley BR; Cai WW; Lozano G; Roop DR. 2007. An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations. J Clin Invest 117(7):1893-901. [PubMed: 17607363]  [MGI Ref ID J:124222]

Caulin C; Nguyen T; Longley MA; Zhou Z; Wang XJ; Roop DR. 2004. Inducible activation of oncogenic K-ras results in tumor formation in the oral cavity. Cancer Res 64(15):5054-8. [PubMed: 15289303]  [MGI Ref ID J:91877]

Cellurale C; Girnius N; Jiang F; Cavanagh-Kyros J; Lu S; Garlick DS; Mercurio AM; Davis RJ. 2012. Role of JNK in mammary gland development and breast cancer. Cancer Res 72(2):472-81. [PubMed: 22127926]  [MGI Ref ID J:181146]

Cellurale C; Sabio G; Kennedy NJ; Das M; Barlow M; Sandy P; Jacks T; Davis RJ. 2011. Requirement of c-Jun NH2-Terminal Kinase for Ras-Initiated Tumor Formation. Mol Cell Biol 31(7):1565-76. [PubMed: 21282468]  [MGI Ref ID J:170101]

Chan G; Cheung LS; Yang W; Milyavsky M; Sanders AD; Gu S; Hong WX; Liu AX; Wang X; Barbara M; Sharma T; Gavin J; Kutok JL; Iscove NN; Shannon KM; Dick JE; Neel BG; Braun BS. 2011. Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells. Blood 117(16):4253-61. [PubMed: 21398220]  [MGI Ref ID J:173832]

Chan IS; Guy CD; Chen Y; Lu J; Swiderska-Syn M; Michelotti GA; Karaca G; Xie G; Kruger L; Syn WK; Anderson BR; Pereira TA; Choi SS; Baldwin AS; Diehl AM. 2012. Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma. Cancer Res 72(24):6344-50. [PubMed: 23066040]  [MGI Ref ID J:193639]

Chan IT; Kutok JL; Williams IR; Cohen S; Kelly L; Shigematsu H; Johnson L; Akashi K; Tuveson DA; Jacks T; Gilliland DG. 2004. Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease. J Clin Invest 113(4):528-38. [PubMed: 14966562]  [MGI Ref ID J:88163]

Chan IT; Kutok JL; Williams IR; Cohen S; Moore S; Shigematsu H; Ley TJ; Akashi K; Le Beau MM; Gilliland DG. 2006. Oncogenic K-ras cooperates with PML-RAR alpha to induce an acute promyelocytic leukemia-like disease. Blood 108(5):1708-15. [PubMed: 16675706]  [MGI Ref ID J:115068]

Chang DR; Martinez Alanis D; Miller RK; Ji H; Akiyama H; McCrea PD; Chen J. 2013. Lung epithelial branching program antagonizes alveolar differentiation. Proc Natl Acad Sci U S A 110(45):18042-51. [PubMed: 24058167]  [MGI Ref ID J:202949]

Charles RP; Iezza G; Amendola E; Dankort D; McMahon M. 2011. Mutationally Activated BRAFV600E Elicits Papillary Thyroid Cancer in the Adult Mouse. Cancer Res 71(11):3863-71. [PubMed: 21512141]  [MGI Ref ID J:172205]

Chen L; Park SM; Tumanov AV; Hau A; Sawada K; Feig C; Turner JR; Fu YX; Romero IL; Lengyel E; Peter ME. 2010. CD95 promotes tumour growth. Nature 465(7297):492-6. [PubMed: 20505730]  [MGI Ref ID J:161953]

Chen Z; Cheng K; Walton Z; Wang Y; Ebi H; Shimamura T; Liu Y; Tupper T; Ouyang J; Li J; Gao P; Woo MS; Xu C; Yanagita M; Altabef A; Wang S; Lee C; Nakada Y; Pena CG; Sun Y; Franchetti Y; Yao C; Saur A; Cameron MD; Nishino M; Hayes DN; Wilkerson MD; Roberts PJ; Lee CB; Bardeesy N; Butaney M; Chirieac LR; Costa DB; Jackman D; Sharpless NE; Castrillon DH; Demetri GD; Janne PA; Pandolfi PP; Cantley LC; Kung AL; Engelman JA; Wong KK. 2012. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature 483(7391):613-7. [PubMed: 22425996]  [MGI Ref ID J:182575]

Cheung AF; Dupage MJ; Dong HK; Chen J; Jacks T. 2008. Regulated expression of a tumor-associated antigen reveals multiple levels of T-cell tolerance in a mouse model of lung cancer. Cancer Res 68(22):9459-68. [PubMed: 19010921]  [MGI Ref ID J:141383]

Chiang MY; Xu L; Shestova O; Histen G; L'heureux S; Romany C; Childs ME; Gimotty PA; Aster JC; Pear WS. 2008. Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras-initiated leukemia. J Clin Invest 118(9):3181-94. [PubMed: 18677410]  [MGI Ref ID J:142160]

Chiao PJ; Ling J. 2011. Kras, Pten, NF-kappaB, and inflammation: dangerous liaisons. Cancer Discov 1(2):103-5. [PubMed: 22586351]  [MGI Ref ID J:193072]

Cho HC; Lai CY; Shao LE; Yu J. 2011. Identification of Tumorigenic Cells in KrasG12D-Induced Lung Adenocarcinoma. Cancer Res 71(23):7250-8. [PubMed: 22088965]  [MGI Ref ID J:178608]

Chugh R; Sangwan V; Patil SP; Dudeja V; Dawra RK; Banerjee S; Schumacher RJ; Blazar BR; Georg GI; Vickers SM; Saluja AK. 2012. A preclinical evaluation of minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med 4(156):156ra139. [PubMed: 23076356]  [MGI Ref ID J:189216]

Clark CE; Hingorani SR; Mick R; Combs C; Tuveson DA; Vonderheide RH. 2007. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res 67(19):9518-27. [PubMed: 17909062]  [MGI Ref ID J:125575]

Clark PE; Polosukhina D; Love H; Correa H; Coffin C; Perlman EJ; de Caestecker M; Moses HL; Zent R. 2011. beta-Catenin and K-RAS synergize to form primitive renal epithelial tumors with features of epithelial Wilms' tumors. Am J Pathol 179(6):3045-55. [PubMed: 21983638]  [MGI Ref ID J:180084]

Collins MA; Brisset JC; Zhang Y; Bednar F; Pierre J; Heist KA; Galban CJ; Galban S; di Magliano MP. 2012. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice. PLoS One 7(12):e49707. [PubMed: 23226501]  [MGI Ref ID J:195686]

Collisson EA; Trejo CL; Silva JM; Gu S; Korkola JE; Heiser LM; Charles RP; Rabinovich BA; Hann B; Dankort D; Spellman PT; Phillips WA; Gray JW; McMahon M. 2012. A central role for RAF-->MEK-->ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov 2(8):685-93. [PubMed: 22628411]  [MGI Ref ID J:193065]

Colvin EK; Susanto JM; Kench JG; Ong VN; Mawson A; Pinese M; Chang DK; Rooman I; O'Toole SA; Segara D; Musgrove EA; Sutherland RL; Apte MV; Scarlett CJ; Biankin AV. 2011. Retinoid signaling in pancreatic cancer, injury and regeneration. PLoS One 6(12):e29075. [PubMed: 22220202]  [MGI Ref ID J:182325]

Connolly MK; Mallen-St Clair J; Bedrosian AS; Malhotra A; Vera V; Ibrahim J; Henning J; Pachter HL; Bar-Sagi D; Frey AB; Miller G. 2010. Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leukoc Biol 87(4):713-25. [PubMed: 20042467]  [MGI Ref ID J:158851]

Cook N; Frese KK; Bapiro TE; Jacobetz MA; Gopinathan A; Miller JL; Rao SS; Demuth T; Howat WJ; Jodrell DI; Tuveson DA. 2012. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med 209(3):437-44. [PubMed: 22351932]  [MGI Ref ID J:182504]

Corcoran RB; Cheng KA; Hata AN; Faber AC; Ebi H; Coffee EM; Greninger P; Brown RD; Godfrey JT; Cohoon TJ; Song Y; Lifshits E; Hung KE; Shioda T; Dias-Santagata D; Singh A; Settleman J; Benes CH; Mino-Kenudson M; Wong KK; Engelman JA. 2013. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell 23(1):121-8. [PubMed: 23245996]  [MGI Ref ID J:194363]

Corcoran RB; Contino G; Deshpande V; Tzatsos A; Conrad C; Benes CH; Levy DE; Settleman J; Engelman JA; Bardeesy N. 2011. STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis. Cancer Res 71(14):5020-9. [PubMed: 21586612]  [MGI Ref ID J:174088]

Cortez-Retamozo V; Etzrodt M; Newton A; Rauch PJ; Chudnovskiy A; Berger C; Ryan RJ; Iwamoto Y; Marinelli B; Gorbatov R; Forghani R; Novobrantseva TI; Koteliansky V; Figueiredo JL; Chen JW; Anderson DG; Nahrendorf M; Swirski FK; Weissleder R; Pittet MJ. 2012. Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci U S A 109(7):2491-6. [PubMed: 22308361]  [MGI Ref ID J:182625]

Cortez-Retamozo V; Etzrodt M; Newton A; Ryan R; Pucci F; Sio SW; Kuswanto W; Rauch PJ; Chudnovskiy A; Iwamoto Y; Kohler R; Marinelli B; Gorbatov R; Wojtkiewicz G; Panizzi P; Mino-Kenudson M; Forghani R; Figueiredo JL; Chen JW; Xavier R; Swirski FK; Nahrendorf M; Weissleder R; Pittet MJ. 2013. Angiotensin II Drives the Production of Tumor-Promoting Macrophages. Immunity 38(2):296-308. [PubMed: 23333075]  [MGI Ref ID J:193393]

Court H; Amoyel M; Hackman M; Lee KE; Xu R; Miller G; Bar-Sagi D; Bach EA; Bergo MO; Philips MR. 2013. Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression. J Clin Invest :. [PubMed: 24216479]  [MGI Ref ID J:204180]

Courtin A; Richards FM; Bapiro TE; Bramhall JL; Neesse A; Cook N; Krippendorff BF; Tuveson DA; Jodrell DI. 2013. Anti-tumour efficacy of capecitabine in a genetically engineered mouse model of pancreatic cancer. PLoS One 8(6):e67330. [PubMed: 23840665]  [MGI Ref ID J:203716]

Curtis SJ; Sinkevicius KW; Li D; Lau AN; Roach RR; Zamponi R; Woolfenden AE; Kirsch DG; Wong KK; Kim CF. 2010. Primary tumor genotype is an important determinant in identification of lung cancer propagating cells. Cell Stem Cell 7(1):127-33. [PubMed: 20621056]  [MGI Ref ID J:162238]

Cutts BA; Sjogren AK; Andersson KM; Wahlstrom AM; Karlsson C; Swolin B; Bergo MO. 2009. Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice. Blood 114(17):3629-32. [PubMed: 19710506]  [MGI Ref ID J:153839]

Daikoku T; Tranguch S; Trofimova IN; Dinulescu DM; Jacks T; Nikitin AY; Connolly DC; Dey SK. 2006. Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res 66(5):2527-31. [PubMed: 16510568]  [MGI Ref ID J:106703]

Dail M; Li Q; McDaniel A; Wong J; Akagi K; Huang B; Kang HC; Kogan SC; Shokat K; Wolff L; Braun BS; Shannon K. 2010. Mutant Ikzf1, KrasG12D, and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents. Proc Natl Acad Sci U S A 107(11):5106-11. [PubMed: 20194733]  [MGI Ref ID J:158752]

Daniluk J; Liu Y; Deng D; Chu J; Huang H; Gaiser S; Cruz-Monserrate Z; Wang H; Ji B; Logsdon CD. 2012. An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice. J Clin Invest 122(4):1519-28. [PubMed: 22406536]  [MGI Ref ID J:184556]

Dasgupta B; Li W; Perry A; Gutmann DH. 2005. Glioma formation in neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Res 65(1):236-45. [PubMed: 15665300]  [MGI Ref ID J:95509]

Dasgupta B; Yi Y; Chen DY; Weber JD; Gutmann DH. 2005. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res 65(7):2755-60. [PubMed: 15805275]  [MGI Ref ID J:97360]

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Sureban SM; May R; Lightfoot SA; Hoskins AB; Lerner M; Brackett DJ; Postier RG; Ramanujam R; Mohammed A; Rao CV; Wyche JH; Anant S; Houchen CW. 2011. DCAMKL-1 Regulates Epithelial-Mesenchymal Transition in Human Pancreatic Cells through a miR-200a-Dependent Mechanism. Cancer Res 71(6):2328-38. [PubMed: 21285251]  [MGI Ref ID J:170354]

Talluri S; Francis SM; Dick FA. 2013. Mutation of the LXCXE binding cleft of pRb facilitates transformation by ras in vitro but does not promote tumorigenesis in vivo. PLoS One 8(8):e72236. [PubMed: 23936539]  [MGI Ref ID J:205769]

Tan X; Carretero J; Chen Z; Zhang J; Wang Y; Chen J; Li X; Ye H; Tang C; Cheng X; Hou N; Yang X; Wong KK. 2013. Loss of p53 attenuates the contribution of IL-6 deletion on suppressed tumor progression and extended survival in Kras-driven murine lung cancer. PLoS One 8(11):e80885. [PubMed: 24260500]  [MGI Ref ID J:206730]

Tang N; Marshall WF; McMahon M; Metzger RJ; Martin GR. 2011. Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Science 333(6040):342-5. [PubMed: 21764747]  [MGI Ref ID J:174194]

Tian H; Callahan CA; DuPree KJ; Darbonne WC; Ahn CP; Scales SJ; de Sauvage FJ. 2009. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A 106(11):4254-9. [PubMed: 19246386]  [MGI Ref ID J:146777]

Timpson P; McGhee EJ; Morton JP; von Kriegsheim A; Schwarz JP; Karim SA; Doyle B; Quinn JA; Carragher NO; Edward M; Olson MF; Frame MC; Brunton VG; Sansom OJ; Anderson KI. 2011. Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53. Cancer Res 71(3):747-57. [PubMed: 21266354]  [MGI Ref ID J:169401]

Tinder TL; Subramani DB; Basu GD; Bradley JM; Schettini J; Million A; Skaar T; Mukherjee P. 2008. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma. J Immunol 181(5):3116-25. [PubMed: 18713982]  [MGI Ref ID J:138959]

Ting DT; Lipson D; Paul S; Brannigan BW; Akhavanfard S; Coffman EJ; Contino G; Deshpande V; Iafrate AJ; Letovsky S; Rivera MN; Bardeesy N; Maheswaran S; Haber DA. 2011. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331(6017):593-6. [PubMed: 21233348]  [MGI Ref ID J:168148]

To MD; Rosario RD; Westcott PM; Banta KL; Balmain A. 2013. Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis. Oncogene 32(34):4028-33. [PubMed: 22945650]  [MGI Ref ID J:203248]

Torchia EC; Caulin C; Acin S; Terzian T; Kubick BJ; Box NF; Roop DR. 2012. Myc, Aurora Kinase A, and mutant p53(R172H) co-operate in a mouse model of metastatic skin carcinoma. Oncogene 31(21):2680-90. [PubMed: 21963848]  [MGI Ref ID J:186136]

Tran K; Risingsong R; Royce DB; Williams CR; Sporn MB; Pioli PA; Gediya LK; Njar VC; Liby KT. 2013. The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer. Carcinogenesis 34(1):199-210. [PubMed: 23042302]  [MGI Ref ID J:193646]

Tran PT; Shroff EH; Burns TF; Thiyagarajan S; Das ST; Zabuawala T; Chen J; Cho YJ; Luong R; Tamayo P; Salih T; Aziz K; Adam SJ; Vicent S; Nielsen CH; Withofs N; Sweet-Cordero A; Gambhir SS; Rudin CM; Felsher DW. 2012. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant kras-induced lung tumorigenesis. PLoS Genet 8(5):e1002650. [PubMed: 22654667]  [MGI Ref ID J:185196]

Trejo CL; Juan J; Vicent S; Sweet-Cordero A; McMahon M. 2012. MEK1/2 inhibition elicits regression of autochthonous lung tumors induced by KRASG12D or BRAFV600E. Cancer Res 72(12):3048-59. [PubMed: 22511580]  [MGI Ref ID J:189336]

Trobridge P; Knoblaugh S; Washington MK; Munoz NM; Tsuchiya KD; Rojas A; Song X; Ulrich CM; Sasazuki T; Shirasawa S; Grady WM. 2009. TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway. Gastroenterology 136(5):1680-8.e7. [PubMed: 19208363]  [MGI Ref ID J:148720]

Tuveson DA; Shaw AT; Willis NA; Silver DP; Jackson EL; Chang S; Mercer KL; Grochow R; Hock H; Crowley D; Hingorani SR; Zaks T; King C; Jacobetz MA; Wang L; Bronson RT; Orkin SH; DePinho RA; Jacks T. 2004. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 5(4):375-87. [PubMed: 15093544]  [MGI Ref ID J:89333]

Tzatsos A; Paskaleva P; Ferrari F; Deshpande V; Stoykova S; Contino G; Wong KK; Lan F; Trojer P; Park PJ; Bardeesy N. 2013. KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. J Clin Invest :. [PubMed: 23321669]  [MGI Ref ID J:194493]

Van Meter ME; Diaz-Flores E; Archard JA; Passegue E; Irish JM; Kotecha N; Nolan GP; Shannon K; Braun BS. 2007. K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells. Blood 109(9):3945-52. [PubMed: 17192389]  [MGI Ref ID J:145335]

Vermeulen L; Morrissey E; van der Heijden M; Nicholson AM; Sottoriva A; Buczacki S; Kemp R; Tavare S; Winton DJ. 2013. Defining stem cell dynamics in models of intestinal tumor initiation. Science 342(6161):995-8. [PubMed: 24264992]  [MGI Ref ID J:205193]

Vernon PJ; Loux TJ; Schapiro NE; Kang R; Muthuswamy R; Kalinski P; Tang D; Lotze MT; Zeh HJ 3rd. 2013. The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells. J Immunol 190(3):1372-9. [PubMed: 23269246]  [MGI Ref ID J:192593]

Vicent S; Chen R; Sayles LC; Lin C; Walker RG; Gillespie AK; Subramanian A; Hinkle G; Yang X; Saif S; Root DE; Huff V; Hahn WC; Sweet-Cordero EA. 2010. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest 120(11):3940-52. [PubMed: 20972333]  [MGI Ref ID J:167562]

Vincent DF; Gout J; Chuvin N; Arfi V; Pommier RM; Bertolino P; Jonckheere N; Ripoche D; Kaniewski B; Martel S; Langlois JB; Goddard-Leon S; Colombe A; Janier M; Van Seuningen I; Losson R; Valcourt U; Treilleux I; Dubus P; Bardeesy N; Bartholin L. 2012. Tif1gamma suppresses murine pancreatic tumoral transformation by a smad4-independent pathway. Am J Pathol 180(6):2214-21. [PubMed: 22469842]  [MGI Ref ID J:184706]

Vincent DF; Yan KP; Treilleux I; Gay F; Arfi V; Kaniewsky B; Marie JC; Lepinasse F; Martel S; Goddard-Leon S; Iovanna JL; Dubus P; Garcia S; Puisieux A; Rimokh R; Bardeesy N; Scoazec JY; Losson R; Bartholin L. 2009. Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet 5(7):e1000575. [PubMed: 19629168]  [MGI Ref ID J:151781]

Wahlstrom AM; Cutts BA; Karlsson C; Andersson KM; Liu M; Sjogren AK; Swolin B; Young SG; Bergo MO. 2007. Rce1 deficiency accelerates the development of K-RAS-induced myeloproliferative disease. Blood 109(2):763-8. [PubMed: 16973961]  [MGI Ref ID J:143675]

Wahlstrom AM; Cutts BA; Liu M; Lindskog A; Karlsson C; Sjogren AK; Andersson KM; Young SG; Bergo MO. 2008. Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease. Blood 112(4):1357-65. [PubMed: 18502828]  [MGI Ref ID J:138426]

Wang Z; Banerjee S; Ahmad A; Li Y; Azmi AS; Gunn JR; Kong D; Bao B; Ali S; Gao J; Mohammad RM; Miele L; Korc M; Sarkar FH. 2011. Activated K-ras and INK4a/Arf Deficiency Cooperate During the Development of Pancreatic Cancer by Activation of Notch and NF-kappaB Signaling Pathways. PLoS One 6(6):e20537. [PubMed: 21673986]  [MGI Ref ID J:174139]

Weinberg F; Hamanaka R; Wheaton WW; Weinberg S; Joseph J; Lopez M; Kalyanaraman B; Mutlu GM; Budinger GR; Chandel NS. 2010. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 107(19):8788-93. [PubMed: 20421486]  [MGI Ref ID J:160298]

Whipple CA; Young AL; Korc M. 2012. A KrasG12D-driven genetic mouse model of pancreatic cancer requires glypican-1 for efficient proliferation and angiogenesis. Oncogene 31(20):2535-44. [PubMed: 21996748]  [MGI Ref ID J:186130]

White AC; Tran K; Khuu J; Dang C; Cui Y; Binder SW; Lowry WE. 2011. Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A 108(18):7425-30. [PubMed: 21502519]  [MGI Ref ID J:172216]

White RA; Neiman JM; Reddi A; Han G; Birlea S; Mitra D; Dionne L; Fernandez P; Murao K; Bian L; Keysar SB; Goldstein NB; Song N; Bornstein S; Han Z; Lu X; Wisell J; Li F; Song J; Lu SL; Jimeno A; Roop DR; Wang XJ. 2013. Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest 123(10):4390-404. [PubMed: 23999427]  [MGI Ref ID J:203922]

Winslow MM; Dayton TL; Verhaak RG; Kim-Kiselak C; Snyder EL; Feldser DM; Hubbard DD; DuPage MJ; Whittaker CA; Hoersch S; Yoon S; Crowley D; Bronson RT; Chiang DY; Meyerson M; Jacks T. 2011. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473(7345):101-4. [PubMed: 21471965]  [MGI Ref ID J:171810]

Won JH; Zhang Y; Ji B; Logsdon CD; Yule DI. 2011. Phenotypic changes in mouse pancreatic stellate cell Ca2+ signaling events following activation in culture and in a disease model of pancreatitis. Mol Biol Cell 22(3):421-36. [PubMed: 21148289]  [MGI Ref ID J:182893]

Wong JC; Zhang Y; Lieuw KH; Tran MT; Forgo E; Weinfurtner K; Alzamora P; Kogan SC; Akagi K; Wolff L; Le Beau MM; Killeen N; Shannon K. 2010. Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies. Blood 115(22):4524-32. [PubMed: 20233966]  [MGI Ref ID J:161558]

Woolfenden S; Zhu H; Charest A. 2009. A Cre/LoxP conditional luciferase reporter transgenic mouse for bioluminescence monitoring of tumorigenesis. Genesis 47(10):659-666. [PubMed: 19603508]  [MGI Ref ID J:153565]

Xia Y; Yeddula N; Leblanc M; Ke E; Zhang Y; Oldfield E; Shaw RJ; Verma IM. 2012. Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol 14(3):257-65. [PubMed: 22327365]  [MGI Ref ID J:185072]

Xiao Z; Jiang Q; Willette-Brown J; Xi S; Zhu F; Burkett S; Back T; Song NY; Datla M; Sun Z; Goldszmid R; Lin F; Cohoon T; Pike K; Wu X; Schrump DS; Wong KK; Young HA; Trinchieri G; Wiltrout RH; Hu Y. 2013. The pivotal role of IKKalpha in the development of spontaneous lung squamous cell carcinomas. Cancer Cell 23(4):527-40. [PubMed: 23597566]  [MGI Ref ID J:197037]

Xu X; Rock JR; Lu Y; Futtner C; Schwab B; Guinney J; Hogan BL; Onaitis MW. 2012. Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma. Proc Natl Acad Sci U S A 109(13):4910-5. [PubMed: 22411819]  [MGI Ref ID J:182218]

Yang X; La Rosa FG; Genova EE; Huber K; Schaack J; Degregori J; Serkova NJ; Li Y; Su LJ; Kessler E; Flaig TW. 2013. Simultaneous activation of Kras and inactivation of p53 induces soft tissue sarcoma and bladder urothelial hyperplasia. PLoS One 8(9):e74809. [PubMed: 24058630]  [MGI Ref ID J:207342]

Yang Y; Iwanaga K; Raso MG; Wislez M; Hanna AE; Wieder ED; Molldrem JJ; Wistuba II; Powis G; Demayo FJ; Kim CF; Kurie JM. 2008. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS ONE 3(5):e2220. [PubMed: 18493606]  [MGI Ref ID J:136369]

Ying H; Elpek KG; Vinjamoori A; Zimmerman SM; Chu GC; Yan H; Fletcher-Sananikone E; Zhang H; Liu Y; Wang W; Ren X; Zheng H; Kimmelman AC; Paik JH; Lim C; Perry SR; Jiang S; Malinn B; Protopopov A; Colla S; Xiao Y; Hezel AF; Bardeesy N; Turley SJ; Wang YA; Chin L; Thayer SP; DePinho RA. 2011. PTEN is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF-kappaB-cytokine network. Cancer Discov 1(2):158-69. [PubMed: 21984975]  [MGI Ref ID J:185636]

Young NP; Crowley D; Jacks T. 2011. Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in Sarcomagenesis. Cancer Res 71(11):4040-7. [PubMed: 21512139]  [MGI Ref ID J:172206]

Zaslavsky A; Baek KH; Lynch RC; Short S; Grillo J; Folkman J; Italiano JE Jr; Ryeom S. 2010. Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood 115(22):4605-13. [PubMed: 20086246]  [MGI Ref ID J:161573]

Zhang J; Liu Y; Beard C; Tuveson DA; Jaenisch R; Jacks TE; Lodish HF. 2007. Expression of oncogenic K-ras from its endogenous promoter leads to a partial block of erythroid differentiation and hyperactivation of cytokine-dependent signaling pathways. Blood 109(12):5238-41. [PubMed: 17317860]  [MGI Ref ID J:145429]

Zhang J; Wang J; Liu Y; Sidik H; Young KH; Lodish HF; Fleming MD. 2009. Oncogenic Kras-induced leukemogeneis: hematopoietic stem cells as the initial target and lineage-specific progenitors as the potential targets for final leukemic transformation. Blood 113(6):1304-14. [PubMed: 19066392]  [MGI Ref ID J:145536]

Zhang N; Bai H; David KK; Dong J; Zheng Y; Cai J; Giovannini M; Liu P; Anders RA; Pan D. 2010. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell 19(1):27-38. [PubMed: 20643348]  [MGI Ref ID J:162628]

Zhang Y; Morris JP 4th; Yan W; Schofield HK; Gurney A; Simeone DM; Millar SE; Hoey T; Hebrok M; Pasca di Magliano M. 2013. Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis. Cancer Res 73(15):4909-4922. [PubMed: 23761328]  [MGI Ref ID J:199468]

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Zhao P; Damerow MS; Stern P; Liu AH; Sweet-Cordero A; Siziopikou K; Neilson JR; Sharp PA; Cheng C. 2013. CD44 promotes Kras-dependent lung adenocarcinoma. Oncogene 32(43):5186-90. [PubMed: 23208496]  [MGI Ref ID J:203236]

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Zheng Y; de la Cruz CC; Sayles LC; Alleyne-Chin C; Vaka D; Knaak TD; Bigos M; Xu Y; Hoang CD; Shrager JB; Fehling HJ; French D; Forrest W; Jiang Z; Carano RA; Barck KH; Jackson EL; Sweet-Cordero EA. 2013. A Rare Population of CD24(+)ITGB4(+)Notch(hi) Cells Drives Tumor Propagation in NSCLC and Requires Notch3 for Self-Renewal. Cancer Cell 24(1):59-74. [PubMed: 23845442]  [MGI Ref ID J:199306]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygotes are embryonic lethal.
Mating System+/+ sibling x Heterozygote         (Female x Male)   21-NOV-08
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Krastm4Tyj  
Price per Pair (US dollars $)Pair Genotype
$302.00Heterozygous for Krastm4Tyj x Wild-type for Krastm4Tyj  
$302.00Wild-type for Krastm4Tyj x Heterozygous for Krastm4Tyj  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Krastm4Tyj  
Price per Pair (US dollars $)Pair Genotype
$392.60Heterozygous for Krastm4Tyj x Wild-type for Krastm4Tyj  
$392.60Wild-type for Krastm4Tyj x Heterozygous for Krastm4Tyj  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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JAX® Mice
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Terms of Use

Terms of Use


General Terms and Conditions


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JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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