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

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Greg Lemke,   The Salk Institute

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of brain lysate. Homozygotes exhibit decreased sensitivity to induced pathological thrombosis resulting in reduced fatal pulmonary embolism (25% of wild-type). Platelet aggregation and clot retraction after thrombin treatment is impaired. Platelet signaling and secretion is also defective. Activity induced seizures can occur in mutant mice over the age of seven months. This mutant mouse strain may be useful in studies of thrombosis and platelet aggregation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 9 and part of exon 10. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting animals were crossed to C57BL/6 mice and then made homozygous. The mice were then backcrossed to C57BL/6 for five generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Tyro3^tm1Grl/Tyro3^tm1Grl

        involves: 129S1/Sv * 129X1/SvJ

• behavior/neurological phenotype
• abnormal seizure response to inducing agent
  • activity-induced seizures are observed in mutants more than 7 months old   (MGI Ref ID J:54681)
• nervous system phenotype
• abnormal seizure response to inducing agent
  • activity-induced seizures are observed in mutants more than 7 months old   (MGI Ref ID J:54681)
• vision/eye phenotype
• *normal* vision/eye phenotype
  • retinas appear normal with no photoreceptor degeneration   (MGI Ref ID J:116526)
• reproductive system phenotype
• *normal* reproductive system phenotype
  • mutant Sertoli cells exhibit normal phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining   (MGI Ref ID J:133455)

View Research Applications

Research Applications

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

Cardiovascular Research
Vascular Defects
      Thrombosis
      platelet defect

Hematological Research
Platelet Defects
      Alterations in platelet aggregation

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tyro3tm1Grl
Allele Name		targeted mutation 1, Greg Lemke
Allele Type		Targeted (knock-out)
Common Name(s)		Rse-; Tyro3;
Mutation Made By		Greg Lemke,   The Salk Institute
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Tyro3, TYRO3 protein tyrosine kinase 3
Chromosome		2
Gene Common Name(s)		AI323366; BYK; Brt; Dtk; Etk-2; RSE; Sky; Tif; brain tyrosine kinase; expressed sequence AI323366;
Molecular Note		A neomycin selection cassette replaced sequences containing exon 9 and part of exon 10. Western blot analysis on brain lysates derived from homozygous mice confirmed that no detectable protein was produced from this allele. [MGI Ref ID J:54681]

Genotyping

Genotyping Information

Genotyping Protocols

Tyro3^tm1Grl, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lu Q; Gore M; Zhang Q; Camenisch T; Boast S; Casagranda F; Lai C; Skinner MK; Klein R; Matsushima GK; Earp HS; Goff SP; Lemke G. 1999. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature 398(6729):723-8. [PubMed: 10227296]  [MGI Ref ID J:54681]

Additional References

Tyro3^tm1Grl related

Angelillo-Scherrer A; Burnier L; Flores N; Savi P; DeMol M; Schaeffer P; Herbert JM; Lemke G; Goff SP; Matsushima GK; Earp HS; Vesin C; Hoylaerts MF; Plaisance S; Collen D; Conway EM; Wehrle-Haller B; Carmeliet P. 2005. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 115(2):237-46. [PubMed: 15650770]  [MGI Ref ID J:95952]

Angelillo-Scherrer A; Burnier L; Lambrechts D; Fish RJ; Tjwa M; Plaisance S; Sugamele R; DeMol M; Martinez-Soria E; Maxwell PH; Lemke G; Goff SP; Matsushima GK; Earp HS; Chanson M; Collen D; Izui S; Schapira M; Conway EM; Carmeliet P. 2008. Role of Gas6 in erythropoiesis and anemia in mice. J Clin Invest 118(2):583-96. [PubMed: 18188450]  [MGI Ref ID J:131177]

Bauer T; Zagorska A; Jurkin J; Yasmin N; Koffel R; Richter S; Gesslbauer B; Lemke G; Strobl H. 2012. Identification of Axl as a downstream effector of TGF-beta1 during Langerhans cell differentiation and epidermal homeostasis. J Exp Med 209(11):2033-47. [PubMed: 23071254]  [MGI Ref ID J:190898]

Chen Y; Wang H; Qi N; Wu H; Xiong W; Ma J; Lu Q; Han D. 2009. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice. Reproduction 138(4):655-66. [PubMed: 19602523]  [MGI Ref ID J:157130]

Deng T; Zhang Y; Chen Q; Yan K; Han D. 2012. Toll-like receptor-mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages. Immunology 135(1):40-50. [PubMed: 22043818]  [MGI Ref ID J:179716]

Lu Q; Lemke G. 2001. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293(5528):306-11. [PubMed: 11452127]  [MGI Ref ID J:70420]

Pierce A; Bliesner B; Xu M; Nielsen-Preiss S; Lemke G; Tobet S; Wierman ME. 2008. Axl and Tyro3 modulate female reproduction by influencing gonadotropin-releasing hormone neuron survival and migration. Mol Endocrinol 22(11):2481-95. [PubMed: 18787040]  [MGI Ref ID J:141251]

Pierce A; Xu M; Bliesner B; Liu Z; Richards J; Tobet S; Wierman ME. 2011. Hypothalamic but not pituitary or ovarian defects underlie the reproductive abnormalities in Axl/Tyro3 null mice. Mol Cell Endocrinol 339(1-2):151-8. [PubMed: 21539887]  [MGI Ref ID J:179535]

Prasad D; Rothlin CV; Burrola P; Burstyn-Cohen T; Lu Q; Garcia de Frutos P; Lemke G. 2006. TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci 33(1):96-108. [PubMed: 16901715]  [MGI Ref ID J:116526]

Radic MZ; Shah K; Zhang W; Lu Q; Lemke G; Hilliard GM. 2006. Heterogeneous nuclear ribonucleoprotein P2 is an autoantibody target in mice deficient for Mer, Axl, and Tyro3 receptor tyrosine kinases. J Immunol 176(1):68-74. [PubMed: 16365397]  [MGI Ref ID J:126253]

Rothlin CV; Ghosh S; Zuniga EI; Oldstone MB; Lemke G. 2007. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131(6):1124-36. [PubMed: 18083102]  [MGI Ref ID J:131447]

Sandahl M; Hunter DM; Strunk KE; Earp HS; Cook RS. 2010. Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation. BMC Dev Biol 10:122. [PubMed: 21192804]  [MGI Ref ID J:167986]

Seitz HM; Camenisch TD; Lemke G; Earp HS; Matsushima GK. 2007. Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol 178(9):5635-42. [PubMed: 17442946]  [MGI Ref ID J:145835]

Shankar SL; O'Guin K; Kim M; Varnum B; Lemke G; Brosnan CF; Shafit-Zagardo B. 2006. Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci 26(21):5638-48. [PubMed: 16723520]  [MGI Ref ID J:182390]

Williams BJ; Craven RR; Earp HS; Kawula TH; Matsushima GK. 2009. TAM receptors are dispensable in the phagocytosis and killing of bacteria. Cell Immunol 259(2):128-34. [PubMed: 19625016]  [MGI Ref ID J:152808]

Williams JC; Wagner NJ; Earp HS; Vilen BJ; Matsushima GK. 2010. Increased hematopoietic cells in the mertk-/- mouse peritoneal cavity: a result of augmented migration. J Immunol 184(12):6637-48. [PubMed: 20483720]  [MGI Ref ID J:161155]

Wu H; Tang H; Chen Y; Wang H; Han D. 2008. High incidence of distal vaginal atresia in mice lacking Tyro3 RTK subfamily. Mol Reprod Dev 75(12):1775-82. [PubMed: 18393392]  [MGI Ref ID J:142166]

Xiong W; Chen Y; Wang H; Wang H; Wu H; Lu Q; Han D. 2008. Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction 135(1):77-87. [PubMed: 18159085]  [MGI Ref ID J:133455]

Ye F; Li Q; Ke Y; Lu Q; Han L; Kaplan HJ; Shao H; Lu Q. 2011. TAM receptor knockout mice are susceptible to retinal autoimmune induction. Invest Ophthalmol Vis Sci 52(7):4239-46. [PubMed: 21467176]  [MGI Ref ID J:181426]

Zhong Z; Wang Y; Guo H; Sagare A; Fernandez JA; Bell RD; Barrett TM; Griffin JH; Freeman RS; Zlokovic BV. 2010. Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region. J Neurosci 30(46):15521-34. [PubMed: 21084607]  [MGI Ref ID J:182379]

Zhu D; Wang Y; Singh I; Bell RD; Deane R; Zhong Z; Sagare A; Winkler EA; Zlokovic BV. 2010. Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115(23):4963-72. [PubMed: 20348395]  [MGI Ref ID J:161551]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	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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