Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names 129-Kras2tm1Tyj/J    (Changed: 25-FEB-05 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+3   Donating Investigator Tyler Jacks,   Massachusetts Institute of Technology

Description
Homozygous mice die at about embryonic day 12-13. They have a hypocellular fetal liver which also displays extensive cell death. They also appear to have a defect in both the hematopoietic cells and their microenvironment.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Kras

008180	129S/Sv-Krastm4Tyj/J
008179	B6.129S4-Krastm4Tyj/J

View Strains carrying other alleles of Kras     (2 strains)

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Kras^tm1Tyj/Kras^tm1Tyj

        involves: 129S2/SvPas

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:43433)
  • on an inbred genetic background, homozygotes die between E12 and E14
  • on a mixed 129S2/SvPas x C57BL/6 genetic background, homozygotes die between E12 and term; the number of viable embryos decreases with increased gestational age, with no mutants surviving past birth
• cardiovascular system phenotype
• pericardial edema (MGI Ref ID J:43433)
  • at E12.5, mutant embryos display signs of edema, esp. in the pericardial space
• embryogenesis phenotype
• reduced embryo size (MGI Ref ID J:43433)
  • homozygotes are morphologically normal up to E10.5, but become readily identifiable by their smaller size at E11.5
• growth/size phenotype
• fetal growth retardation (MGI Ref ID J:43433)
  • on a mixed 129S2/SvPas x C57BL/6 genetic background, homozygotes show a more severe developmental delay, which is both coordinate and non-coordinate in nature
  • at E18.5, some homozygotes of mixed background have developed limbs, skin, tail, and whiskers associated with E17.5-18.5, but eyes associated with E15.5
  • beginning at E11.5, mutant embryos of an inbred genetic background exhibit a developmental delay ranging from 0.5 to 3 gestational days
  • at E15.5 or older, a small % of homozygotes of mixed background display a non-coordinate development of internal organs
• reduced embryo size (MGI Ref ID J:43433)
  • homozygotes are morphologically normal up to E10.5, but become readily identifiable by their smaller size at E11.5
• hematopoietic system phenotype
• abnormal hematopoiesis (MGI Ref ID J:43433)
  • mutant embryos display a perturbed hematopoietic microenvironment in the fetal liver despite normal differentiation of hematopoietic progenitors in vitro or upon transplant into lethally irradiated recipients
• anemia (MGI Ref ID J:43433)
  • at E12.5, mutant embryos are anemic
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:43433)
  • at E12.5, mutant embryos display signs of edema, esp. in the pericardial space
• liver/biliary system phenotype
• pale liver (MGI Ref ID J:43433)
  • at E12.5, mutant livers are much paler than wild-type livers
• small liver (MGI Ref ID J:43433)
  • at E12.5, mutant livers are significantly smaller than wild-type livers
• liver hypoplasia (MGI Ref ID J:43433)
  • at E12.5, mutant livers show a 2- to 8-fold reduction in total cell number relative to wild-type livers
• skin/coat/nails phenotype
• pallor (MGI Ref ID J:43433)
  • at E12.5, homozygotes are pale with reduced superficial vasculature
• cellular phenotype
• increased apoptosis (MGI Ref ID J:43433)
  • at E12.5, mutant fetal livers contain pyknotic nuclei in the distal portion of hepatic lobe
  • in severely affected embryos, apoptotic cells are detected throughout the fetal liver

View Research Applications

Research Applications

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

Kras related

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

Kras^tm1Tyj related

Cancer Research
Genes Regulating Growth and Proliferation
Oncogenes

Developmental Biology Research
Internal/Organ Defects (liver)

Hematological Research
Hematopoietic Defects

Internal/Organ Research
Liver Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Krastm1Tyj
Allele Name		targeted mutation 1, Tyler Jacks
Allele Type		Targeted (knock-out)
Common Name(s)		K-ras-; K-rasKO; K-rastm1;
Mutation Made By		Tyler Jacks,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
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; c-Ki-ras; expressed sequence AI929937; p21;
Molecular Note		Exon 1 was replaced by a neomycin cassette. [MGI Ref ID J:43433]

Genotyping

Genotyping Information

Genotyping Protocols

Kras^tm1Tyj, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Johnson L; Greenbaum D; Cichowski K; Mercer K; Murphy E; Schmitt E ; Bronson RT ; Umanoff H ; Edelmann W ; Kucherlapati R ; Jacks T. 1997. K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev 11(19):2468-81. [PubMed: 9334313]  [MGI Ref ID J:43433]

Additional References

Liu ML; Shibata MA; Von Lintig FC; Wang W; Cassenaer S; Boss GR; Green JE. 2001. Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice. Oncogene 20(16):2044-9. [PubMed: 11360188]  [MGI Ref ID J:69250]

Kras^tm1Tyj related

Costa RM; Federov NB; Kogan JH; Murphy GG; Stern J; Ohno M; Kucherlapati R; Jacks T; Silva AJ. 2002. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415(6871):526-30. [PubMed: 11793011]  [MGI Ref ID J:74257]

Khalaf WF; White H; Wenning MJ; Orazi A; Kapur R; Ingram DA. 2005. K-Ras is essential for normal fetal liver erythropoiesis. Blood 105(9):3538-41. [PubMed: 15644420]  [MGI Ref ID J:105055]

Liu ML; Shibata MA; Von Lintig FC; Wang W; Cassenaer S; Boss GR; Green JE. 2001. Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice. Oncogene 20(16):2044-9. [PubMed: 11360188]  [MGI Ref ID J:69250]

Ohno M; Frankland PW; Chen AP; Costa RM; Silva AJ. 2001. Inducible, pharmacogenetic approaches to the study of learning and memory. Nat Neurosci 4(12):1238-43. [PubMed: 11713472]  [MGI Ref ID J:109368]

Patek CE; Arends MJ; Wallace WA; Luo F; Hagan S; Brownstein DG; Rose L; Devenney PS; Walker M; Plowman SJ; Berry RL; Kolch W; Sansom OJ; Harrison DJ; Hooper ML. 2008. Mutationally activated K-ras 4A and 4B both mediate lung carcinogenesis. Exp Cell Res 314(5):1105-14. [PubMed: 18062963]  [MGI Ref ID J:133431]

Takahashi C; Contreras B; Bronson RT; Loda M; Ewen ME. 2004. Genetic Interaction between Rb and K-ras in the Control of Differentiation and Tumor Suppression. Mol Cell Biol 24(23):10406-15. [PubMed: 15542848]  [MGI Ref ID J:94087]

Wang Y; Zhang Z; Lubet R; You M. 2005. Tobacco smoke-induced lung tumorigenesis in mutant A/J mice with alterations in K-ras, p53, or Ink4a/Arf. Oncogene 24(18):3042-9. [PubMed: 15846305]  [MGI Ref ID J:98054]

Wang Y; Zhang Z; Lubet RA; You M. 2006. A mouse model for tumor progression of lung cancer in ras and p53 transgenic mice. Oncogene 25(8):1277-80. [PubMed: 16247444]  [MGI Ref ID J:107333]

Wang Y; Zhang Z; Yao R; Jia D; Wang D; Lubet RA; You M. 2006. Prevention of lung cancer progression by bexarotene in mouse models. Oncogene 25(9):1320-9. [PubMed: 16247446]  [MGI Ref ID J:107330]

Wikenheiser-Brokamp KA. 2006. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol Life Sci 63(7-8):767-80. [PubMed: 16465443]  [MGI Ref ID J:108542]

Yan Y; Tan Q; Wang Y; Wang D; Jin M; Gordon T; Lubet RA; You M. 2007. Enhanced lung tumor development in tobacco smoke-exposed p53 transgenic and Kras2 heterozygous deficient mice. Inhal Toxicol 19 Suppl 1:183-7. [PubMed: 17886066]  [MGI Ref ID J:138096]

Zhang J; Lodish HF. 2005. Identification of K-ras as the major regulator for cytokine-dependent Akt activation in erythroid progenitors in vivo. Proc Natl Acad Sci U S A 102(41):14605-10. [PubMed: 16203968]  [MGI Ref ID J:102491]

Zhang Z; Wang Y; Vikis HG; Johnson L; Liu G; Li J; Anderson MW; Sills RC; Hong HL; Devereux TR; Jacks T; Guan KL; You M. 2001. Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nat Genet 29(1):25-33. [PubMed: 11528387]  [MGI Ref ID J:71546]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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

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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

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.

For additional Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

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