Description

Strain Information

Former Names 129S4-Krastm4Tyj/J    (Changed: 02-APR-08 ) Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
This 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 tamoxifen inducible Cre recombinase (see Stock No. 008463 for example), this mutant mouse strain may be useful in studies of tumorigenesis in the colon.

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 crossed to 129S4/SvJae for more than 10 generations by the donating laboratory which verified correct orientation by Southern assays involving 5' and 3' external and internal probes.

Related Strains

Strains carrying other alleles of Kras

002674

129-Krastm1Tyj/J

View Strains carrying other alleles of Kras     (1 strain)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Kras^tm4Tyj/Kras^tm4Tyj

        Background Not Specified

• tumorigenesis
• lung tumor (MGI Ref ID J:119477)
  • 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

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

Kras^tm4Tyj/Kras⁺ Tg(Fabp1-cre)1Jig/0

        involves: FVB/N   (conditional)

• digestive/alimentary phenotype
• abnormal colon morphology (MGI Ref ID J:89333)
  • diffuse hyperplasia and dysplasia of the colonic crypts is seen by 4 weeks of age
  • increased proliferation of the hyperplastic and dysplastic colonic epithelium is seen in mutants

Kras^tm4Tyj/Kras⁺ Tg(MMTV-cre)4Mam/0

        involves: FVB   (conditional)

• endocrine/exocrine gland phenotype
• abnormal salivary gland morphology (MGI Ref ID J:89333)
  • submandibular gland hyperplasia is seen in these mutants
• digestive/alimentary phenotype
• abnormal salivary gland morphology (MGI Ref ID J:89333)
  • submandibular gland hyperplasia is seen in these mutants

Kras^tm4Tyj/Kras⁺ Tg(Mx1-cre)1Cgn/?

        involves: 129S4/SvJae * C57BL/6 * BALB/c   (conditional)

• life span-post-weaning/aging
• premature death (MGI Ref ID J:88163)
  • survival for around 35 days after pI-pC treatment
  • survival of around 58 days even without pI-pC treatment
• tumorigenesis
• increased tumor incidence (MGI Ref ID J:88163)
• lung adenoma (MGI Ref ID J:88163)
  • nodules in lungs
• papilloma (MGI Ref ID J:88163)
  • squamous papillomas
• thymic lymphoma (MGI Ref ID J:88163)
  • thymic T-cell lymphomas
• growth/size phenotype
• cachexia (MGI Ref ID J:88163)
  • becoming emaciated
• hematopoietic system phenotype
• abnormal hematopoiesis (MGI Ref ID J:88163)
  • develop lethal hematopoietic disease
• abnormal myelopoiesis (MGI Ref ID J:88163)
  • myeloproliferative phenotype
  • myeloid hyperplasia of bone marrow
• abnormal red blood cell (MGI Ref ID J:88163)
• decreased hematocrit (MGI Ref ID J:88163)
  • average hematocrit of 27%
• extramedullary hematopoiesis (MGI Ref ID J:88163)
  • expansion of red pulp in spleen by granulocyte/monocyte lineages in 11 out of 16 cases
  • erythroid expansion was seen in red pulp of spleen in 5 of 16 cases
• increased leukocyte cell number (MGI Ref ID J:88163)
  • leukocytosis, usually involving increases in granulocytes
• immune system phenotype
• abnormal myelopoiesis (MGI Ref ID J:88163)
  • myeloproliferative phenotype
  • myeloid hyperplasia of bone marrow
• increased leukocyte cell number (MGI Ref ID J:88163)
  • leukocytosis, usually involving increases in granulocytes
• liver/biliary system phenotype
• abnormal liver/biliary system morphology (MGI Ref ID J:88163)
  • perivascular and periportal infiltration in liver by myeloid and erythroid cells similar to what is seen in spleen
• skin/coat/nails phenotype
• ruffled hair (MGI Ref ID J:88163)
  • ruffled fur

Kras^tm4Tyj/Kras^tm4Tyj Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0

        involves: 129 * C57BL/6   (conditional)

• respiratory system phenotype
• abnormal bronchus morphology (MGI Ref ID J:119477)
  • 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
• abnormal lung epithelium morphology (MGI Ref ID J:119477)
  • branching defect originates in epithelium rather than mesenchyme
• abnormal tracheal-bronchial branching morphogenesis (MGI Ref ID J:119477)
  • with doxycycline treatment beginning at E6.5, a dramatic lung branching defect is observed
  • 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

Kras^tm4Tyj/Kras^tm4Tyj Tg(Tek-cre)12Flv/0

        involves: C3H * C57BL/6   (conditional)

• embryogenesis phenotype
• *normal* embryogenesis phenotype (MGI Ref ID J:119477)
  • mutants show normal vascularization of the yolk sac and placental labyrinth

Gt(ROSA)26Sor^{tm1(cre/ESR1)Tyj}/Gt(ROSA)26Sor⁺ Kras^tm4Tyj/Kras⁺

        involves: 129S4/SvJae   (conditional)

• digestive/alimentary phenotype
• abnormal intestinal epithelium morphology (MGI Ref ID J:132357)
  • adult mice develop widespread hyperplasia throughout the colonic epithelium
• abnormal intestinal goblet cells (MGI Ref ID J:132357)
  • large, prominent goblet cells develop in the colon in adult mice
• abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:132357)
  • hyperplasia is typified by lengthening of the crypts in adult mice
• endocrine/exocrine gland phenotype
• abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:132357)
  • hyperplasia is typified by lengthening of the crypts in adult mice

Kras^tm4Tyj/Kras^tm4Tyj Meox2^tm1(cre)Sor/Meox2⁺

        Background Not Specified   (conditional)

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

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence (Other Tissues/Organs: lung)

Developmental Biology Research
Embryonic Lethality (Homozygous)

Research Tools
Cre-lox System (loxP-flanked Sequences)

Kras related

Cancer Research
Genes Regulating Growth and Proliferation
Increased Tumor Incidence (Adenomas: lung, induced)
Increased Tumor Incidence (Other Tissues/Organs: lung, induced)
Oncogenes

Developmental Biology Research
Internal/Organ Defects (liver)

Hematological Research
Hematopoietic Defects

Internal/Organ Research
Liver Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Krastm4Tyj
Allele Name		targeted mutation 4, Tyler Jacks
Allele Type		Targeted (knock-in)
Common Name(s)		K-rasLSL; Kras2tm14Tyj; KrasG12D; KrasLox; LSL-K-ras G12D; LSL-KrasG12D;
Mutation Made By		Tyler Jacks,   Massachusetts Institute of Technology
Gene Symbol and Name		Kras, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
Chromosome		6
Gene Common Name(s)		AI929937; C-K-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; K-ras; KI-RAS; KRAS1; KRAS2; Kirsten rat sarcoma oncogene 2, expressed; Kras-2; Kras2; NS3; RASK2; expressed sequence AI929937;
General Note		Mice heterozygous for Krastm4Tyj and Ptf1atm1.1(cre)Cvw and homozygous for Tgfbr2tm1.2Hlm exhibit phenotypic similarity to human syndrome: pancreatic ductal adenocarcinoma (PDAC) (J:116129).
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

Genotyping Protocols

Kras^tm4Tyj, STD PCR, vers. 1
Kras^tm4Tyj, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

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

Kras^tm4Tyj related

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Dasgupta B; Yi Y; Hegedus B; Weber JD; Gutmann DH. 2005. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Res 65(21):9843-50. [PubMed: 16267007]  [MGI Ref ID J:102692]

Dinulescu DM; Ince TA; Quade BJ; Shafer SA; Crowley D; Jacks T. 2005. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11(1):63-70. [PubMed: 15619626]  [MGI Ref ID J:96296]

Fan HY; Shimada M; Liu Z; Cahill N; Noma N; Wu Y; Gossen J; Richards JS. 2008. Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation. Development 135(12):2127-37. [PubMed: 18506027]  [MGI Ref ID J:137019]

Gades NM; Ohash A; Mills LD; Rowley MA; Predmore KS; Marler RJ; Couch FJ. 2008. Spontaneous vulvar papillomas in a colony of mice used for pancreatic cancer research. Comp Med 58(3):271-5. [PubMed: 18589869]  [MGI Ref ID J:140431]

Haigis KM; Kendall KR; Wang Y; Cheung A; Haigis MC; Glickman JN; Niwa-Kawakita M; Sweet-Cordero A; Sebolt-Leopold J; Shannon KM; Settleman J; Giovannini M; Jacks T. 2008. Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon. Nat Genet :. [PubMed: 18372904]  [MGI Ref ID J:132357]

Hegedus B; Dasgupta B; Shin JE; Emnett RJ; Hart-Mahon EK; Elghazi L; Bernal-Mizrachi E; Gutmann DH. 2007. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell 1(4):443-57. [PubMed: 18371380]  [MGI Ref ID J:139866]

Hegedus B; Yeh TH; Lee da Y; Emnett RJ; Li J; Gutmann DH. 2008. Neurofibromin regulates somatic growth through the hypothalamic-pituitary axis. Hum Mol Genet 17(19):2956-66. [PubMed: 18614544]  [MGI Ref ID J:138868]

Hingorani SR; Petricoin EF; Maitra A; Rajapakse V; King C; Jacobetz MA; Ross S; Conrads TP; Veenstra TD; Hitt BA; Kawaguchi Y; Johann D; Liotta LA; Crawford HC; Putt ME; Jacks T; Wright CV; Hruban RH; Lowy AM; Tuveson DA. 2003. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4(6):437-50. [PubMed: 14706336]  [MGI Ref ID J:87973]

Hingorani SR; Wang L; Multani AS; Combs C; Deramaudt TB; Hruban RH; Rustgi AK; Chang S; Tuveson DA. 2005. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7(5):469-83. [PubMed: 15894267]  [MGI Ref ID J:98936]

Ijichi H; Chytil A; Gorska AE; Aakre ME; Fujitani Y; Fujitani S; Wright CV; Moses HL. 2006. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev 20(22):3147-60. [PubMed: 17114585]  [MGI Ref ID J:116129]

Iwanaga K; Yang Y; Raso MG; Ma L; Hanna AE; Thilaganathan N; Moghaddam S; Evans CM; Li H; Cai WW; Sato M; Minna JD; Wu H; Creighton CJ; Demayo FJ; Wistuba II; Kurie JM. 2008. Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer. Cancer Res 68(4):1119-27. [PubMed: 18281487]  [MGI Ref ID J:131721]

Izeradjene K; Combs C; Best M; Gopinathan A; Wagner A; Grady WM; Deng CX; Hruban RH; Adsay NV; Tuveson DA; Hingorani SR. 2007. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 11(3):229-43. [PubMed: 17349581]  [MGI Ref ID J:119990]

Jackson EL; Olive KP; Tuveson DA; Bronson R; Crowley D; Brown M; Jacks T. 2005. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res 65(22):10280-8. [PubMed: 16288016]  [MGI Ref ID J:103407]

Ji H; Houghton AM; Mariani TJ; Perera S; Kim CB; Padera R; Tonon G; McNamara K; Marconcini LA; Hezel A; El-Bardeesy N; Bronson RT; Sugarbaker D; Maser RS; Shapiro SD; Wong KK. 2006. K-ras activation generates an inflammatory response in lung tumors. Oncogene 25(14):2105-12. [PubMed: 16288213]  [MGI Ref ID J:107260]

Ji H; Ramsey MR; Hayes DN; Fan C; McNamara K; Kozlowski P; Torrice C; Wu MC; Shimamura T; Perera SA; Liang MC; Cai D; Naumov GN; Bao L; Contreras CM; Li D; Chen L; Krishnamurthy J; Koivunen J; Chirieac LR; Padera RF; Bronson RT; Lindeman NI; Christiani DC; Lin X; Shapiro GI; Janne PA; Johnson BE; Meyerson M; Kwiatkowski DJ; Castrillon DH; Bardeesy N; Sharpless NE; Wong KK. 2007. LKB1 modulates lung cancer differentiation and metastasis. Nature 448(7155):807-10. [PubMed: 17676035]  [MGI Ref ID J:124682]

Kim CF; Jackson EL; Kirsch DG; Grimm J; Shaw AT; Lane K; Kissil J; Olive KP; Sweet-Cordero A; Weissleder R; Jacks T. 2005. Mouse models of human non-small-cell lung cancer: raising the bar. Cold Spring Harb Symp Quant Biol 70:241-50. [PubMed: 16869760]  [MGI Ref ID J:116813]

Kindler T; Cornejo MG; Scholl C; Liu J; Leeman DS; Haydu JE; Frohling S; Lee BH; Gilliland DG. 2008. K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to gamma-secretase inhibitors. Blood 112(8):3373-82. [PubMed: 18663146]  [MGI Ref ID J:140221]

Kirsch DG; Dinulescu DM; Miller JB; Grimm J; Santiago PM; Young NP; Nielsen GP; Quade BJ; Chaber CJ; Schultz CP; Takeuchi O; Bronson RT; Crowley D; Korsmeyer SJ; Yoon SS; Hornicek FJ; Weissleder R; Jacks T. 2007. A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13(8):992-7. [PubMed: 17676052]  [MGI Ref ID J:125101]

Kissil JL; Walmsley MJ; Hanlon L; Haigis KM; Bender Kim CF; Sweet-Cordero A; Eckman MS; Tuveson DA; Capobianco AJ; Tybulewicz VL; Jacks T. 2007. Requirement for Rac1 in a K-ras Induced Lung Cancer in the Mouse. Cancer Res 67(17):8089-94. [PubMed: 17804720]  [MGI Ref ID J:124883]

Kojima K; Vickers SM; Adsay NV; Jhala NC; Kim HG; Schoeb TR; Grizzle WE; Klug CA. 2007. Inactivation of Smad4 Accelerates KrasG12D-Mediated Pancreatic Neoplasia. Cancer Res 67(17):8121-30. [PubMed: 17804724]  [MGI Ref ID J:124882]

Kumar MS; Lu J; Mercer KL; Golub TR; Jacks T. 2007. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673-7. [PubMed: 17401365]  [MGI Ref ID J:123829]

Lu SL; Herrington H; Reh D; Weber S; Bornstein S; Wang D; Li AG; Tang CF; Siddiqui Y; Nord J; Andersen P; Corless CL; Wang XJ. 2006. Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma. Genes Dev 20(10):1331-42. [PubMed: 16702406]  [MGI Ref ID J:108711]

Pasca di Magliano M; Biankin AV; Heiser PW; Cano DA; Gutierrez PJ; Deramaudt T; Segara D; Dawson AC; Kench JG; Henshall SM; Sutherland RL; Dlugosz A; Rustgi AK; Hebrok M. 2007. Common activation of canonical wnt signaling in pancreatic adenocarcinoma. PLoS ONE 2(11):e1155. [PubMed: 17982507]  [MGI Ref ID J:130408]

Pasca di Magliano M; Sekine S; Ermilov A; Ferris J; Dlugosz AA; Hebrok M. 2006. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 20(22):3161-73. [PubMed: 17114586]  [MGI Ref ID J:116111]

Perera SA; Maser RS; Xia H; McNamara K; Protopopov A; Chen L; Hezel AF; Kim CF; Bronson RT; Castrillon DH; Chin L; Bardeesy N; Depinho RA; Wong KK. 2008. Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis 29(4):747-53. [PubMed: 18283039]  [MGI Ref ID J:133322]

Seidler B; Schmidt A; Mayr U; Nakhai H; Schmid RM; Schneider G; Saur D. 2008. A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors. Proc Natl Acad Sci U S A 105(29):10137-42. [PubMed: 18621715]  [MGI Ref ID J:140423]

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Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygotes are embryonic lethal.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.
P53 Mice are subject to U.S. 5,569,824 and corresponding license requirements.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.