FVB.129P2(Cg)-Mst1r^{tm2(Mst1r*)Sew}/J

Stock number: 026434
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools, Virology Research

Description

These FL-RON mutant mice express only the full-length protein, and do not express the truncated isoform. They are suitable for use in studies of the role of the alternate forms of this receptor tyrosine kinase in the innate immune response.

Detailed description

The Mst1r gene encodes for a receptor tyrosine kinase that binds the macrophage-stimulating protein and is involved in wound healing (epithelial cell migration) and innate immune response. These mice carry a mutation of the Mst1r gene in which the alternative truncated short-length protein is not expressed, only the full length form of the protein is expressed. No short-length/truncated gene product (mRNA) is detected by RT-PCR analysis of bone marrow, spleen or testis from homozygotes, and Northern blot analysis of testicular RNA from homozygotes. Mice homozygous for the mutation are less susceptible to Friend leukemia viral infection. When challenged with ConA induced T-cell mediated acute liver injury, homozygotes exhibit higher levels of serum IFN-gamma and have a more severe liver injury response when compared to wildtype controls. Mice that are homozygous for the targeted mutation are viable and fertile.

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. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing 2.0-kb cDNA fragment encoding exons 9 through 19 and a NEO cassette was used to disrupt exons 8 through 12. The construct was electroporated into 129P2/OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were bred to NIH Black Swiss to achieve germline transmission. The mice were then backcrossed to FVB for more than 8 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to FVB/NJ (Stock No. 001800) at least once to establish the colony.

Allele

Symbol: Mst1r^{tm2(Mst1r*)Sew}
Name: targeted mutation 2, Susan E Waltz
MGI accession ID: MGI:5607440
Generation method: Targeted
Attributes: Modified isoform(s)
Marker symbol: Mst1r
Marker name: macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
Chromosome: 9
Strain of origin: 129P2/OlaHsd
Molecular note: A targeting vector containing a 2.0-kb cDNA fragment encoding exons 9 through 19 and a neo cassette was used to disrupt exons 8 through 12. Elimination of the alternative transcription start site in intron 10 results in expression of the full length (FL) mRNA transcript, but not the short-form (SF) transcript. RT-PCR analysis on spleen, bone marrow, and testis detected only long form transcript.