Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   01-SEP-10 Species laboratory mouse Generation F?+N1F5 (16-SEP-12) Generation Definitions   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. In response to endotoxin, homozygotes exhibit an increase in spleen size and a decrease in monocyte response. Retinal photoreceptor epithelial cells fail to phagocytose outer segment membranes resulting in complete photoreceptor degeneration and blindness.
When combined with the mutations Tyro3^tm1Grl (Stock No. 007937) and Axl^tm1Grl (Stock No. 011121) mice exhibit a lymphoproliferative disorder, autoimmunity, increased apoptosis in multiple tissues, abnormal spermatogenesis and reduced (in females) fertility or infertility (in males). This mutant mouse strain may be useful in studies of autoimmunity, germ cell development homeostatic regulation and apoptosis.

Development
A targeting vector was designed to introduce a neomycin resistance cassette into exon 18, the last exon encoding the 3' end of the kinase domain. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were intercrossed to generate homozygotes. Upon arrival at The Jackson Laboratory, mutant mice were bred to B6129SF2/J inbred mice (Stock No. 101045) to establish the colony.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mertk

004110

C57BL/6J-Mertknmf12/J

View Strains carrying other alleles of Mertk     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Retinitis Pigmentosa 38; RP38   (MERTK)

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.

Mertk^tm1Grl/Mertk^tm1Grl

        Background Not Specified

• immune system phenotype
• enlarged spleen
  • 2-fold increase in spleen size   (MGI Ref ID J:54681)
• vision/eye phenotype
• abnormal photoreceptor outer segment morphology
  • outer segment tips of the retina are aberrantly extended into the RPE cell layer at P17 such that by P21, there is a 33% increase in overall outer segment length relative to wild-type   (MGI Ref ID J:116526)
• • disorganized photoreceptor outer segment
    • by P35, the outer segment layer becomes very disordered compared to wild-type   (MGI Ref ID J:116526)
• abnormal retinal pigment epithelium morphology
  • retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments   (MGI Ref ID J:116526)
• blindness   (MGI Ref ID J:116526)
• retinal photoreceptor degeneration
  • by 2 months of age, nearly all photoreceptors die by apoptosis   (MGI Ref ID J:116526)
• nervous system phenotype
• abnormal photoreceptor outer segment morphology
  • outer segment tips of the retina are aberrantly extended into the RPE cell layer at P17 such that by P21, there is a 33% increase in overall outer segment length relative to wild-type   (MGI Ref ID J:116526)
• • disorganized photoreceptor outer segment
    • by P35, the outer segment layer becomes very disordered compared to wild-type   (MGI Ref ID J:116526)
• retinal photoreceptor degeneration
  • by 2 months of age, nearly all photoreceptors die by apoptosis   (MGI Ref ID J:116526)
• hematopoietic system phenotype
• enlarged spleen
  • 2-fold increase in spleen size   (MGI Ref ID J:54681)
• pigmentation phenotype
• abnormal retinal pigment epithelium morphology
  • retinal pigment epithelial cells are unable to phagocytose the distal ends of the photoreceptor outer segments   (MGI Ref ID J:116526)
• reproductive system phenotype
• decreased Sertoli cell phagocytosis
  • mutant Sertoli cells show a 35% decrease in 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)
• vagina atresia   (MGI Ref ID J:142166)

View Research Applications

Research Applications

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

Apoptosis Research

Immunology, Inflammation and Autoimmunity Research
Autoimmunity

Reproductive Biology Research

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mertktm1Grl
Allele Name		targeted mutation 1, Greg Lemke
Allele Type		Targeted (knock-out)
Common Name(s)		Mer-; Mertk-;
Mutation Made By		Greg Lemke,   The Salk Institute
Strain of Origin		129P2/OlaHsd
Gene Symbol and Name		Mertk, c-mer proto-oncogene tyrosine kinase
Chromosome		2
Gene Common Name(s)		Eyk; MER; Mer; Nyk; RP38; Tyro 12; c-mer; c-mer proto-oncogene; neuroscience mutagenesis facility, 12; nmf12; rdy;
Molecular Note		A neomycin selection cassette replaced a genomic fragment containing exon 18 of the gene, which encodes part of the kinase domain known to be essential for tyrosine kinase function. An RNase protection assay demonstrated that a mutant transcript was expressed that lacked the deleted sequences. [MGI Ref ID J:54681]

Genotyping

Genotyping Information

Genotyping Protocols

Mertk^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

Mertk^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]

Khan TN; Wong EB; Soni C; Rahman ZS. 2013. Prolonged Apoptotic Cell Accumulation in Germinal Centers of Mer-Deficient Mice Causes Elevated B Cell and CD4+ Th Cell Responses Leading to Autoantibody Production. J Immunol 190(4):1433-46. [PubMed: 23319738]  [MGI Ref ID J:193315]

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]

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]

Shang T; Zhang X; Wang T; Sun B; Deng T; Han D. 2011. Toll-like receptor-initiated testicular innate immune responses in mouse leydig cells. Endocrinology 152(7):2827-36. [PubMed: 21540291]  [MGI Ref ID J:174897]

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; Han L; Lu Q; Dong W; Chen Z; Shao H; Kaplan HJ; Li Q; Lu Q. 2011. Retinal self-antigen induces a predominantly Th1 effector response in Axl and Mertk double-knockout mice. J Immunol 187(8):4178-86. [PubMed: 21918185]  [MGI Ref ID J:179310]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   01-SEP-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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