FVB.129(B6)-Mertk^tm1Grl/AmenJ

Stock number: 037519
Product name: Mer^-
Strain synonyms: Mertk KO
Research areas: Apoptosis Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research, Sensorineural Research

Description

This knock-out mutation of the MER proto-oncogene tyrosine kinase gene (Mertk) exhibits photoreceptor degeneration and abnormal endotoxin response. In combination with mutations in other receptor tyrosine kinases, this Mer^- strain may be useful in studying autoimmunity, germ cell development, homeostatic regulation and apoptosis.

Stock No. 037519 is a FVB/N-congenic Mer^- mouse line. Of note, the same Mer^- allele is also available on a mixed genetic background as Stock No. 011122.

Detailed description

MER proto-oncogene tyrosine kinase (MERTK) is a transmembrane receptor that belongs to the TAM family of receptor tyrosine kinases and is highly expressed in monocytes/macrophages, testis and epithelial cells, including the retinal pigment epithelium. Mice that are homozygous for the Mertk knock-out allele are viable, fertile and do not display an overt phenotype. This Mer^- knock-out strain may be useful in studies of autoimmunity, germ cell development, homeostatic regulation and apoptosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these FVB/N congenic mice could vary from that originally described on a mixed genetic background. We may modify the strain description if necessary, as published results become available.

Development

A targeting vector was designed by Dr. H. Shelton Earp (University of North Carolina, Chapel Hill) to introduce a neomycin resistance cassette into exon 18 (the last exon encoding the 3' end of the kinase domain) of the c-mer proto-oncogene tyrosine kinase gene (Mertk; Mer) on chromosome 2. 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. Before 2006, mice were sent to Dr. Greg Lemke (The Salk Institute), who later sent them to The Jackson Laboratory in 2010. Upon arrival, mutant mice were bred to B6129SF2/J inbred mice (Stock No. 101045) to establish the colony. The resulting Mer- mouse line, on a mixed B6;129 background, is Stock No. 011122.

Dr. Sarah Amend was gifted Mer^- animals, on a mixed genetic background, and then backcrossed these mice to FVB-Tg(ARR2/Pbsn-MYC)7Key/Nci (NCI Mouse Repository Strain Number 01XK8) mice for at least six generations using a speed congenic protocol. The donating laboratory has confirmed that these mice are >99.5% FVB/N. FVB/N-congenic donor males supplied to the Jackson Laboratory only carry the Mer^- allele. The resulting FVB/N-congenic strain is called FVB.129(B6)-Mertk^tm1Grl/AmenJ, Stock No. 037519. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Mertk^tm1Grl
Name: targeted mutation 1, Greg Lemke
MGI accession ID: MGI:2387765
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Mertk
Marker name: c-mer proto-oncogene tyrosine kinase
Chromosome: 2
Strain of origin: 129P2/OlaHsd
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.