FVB;129P2-Met^tm1Sst/J

Stock number: 016974
Product name: c-met^fl
Research areas: Cancer Research, Developmental Biology Research, Neurobiology Research, Research Tools

Description

These c-met^fl/fl floxed mutant mice possess loxP sites flanking exon 16 of the met proto-oncogene (Met) sequence. This strain may be useful for studying neuronal growth and development in neuropsychiatric diseases such as schizophrenia and autism.

Detailed description

These c-met^fl/fl floxed mutant mice possess loxP sites flanking exon 16 of the met proto-oncogene (Met) sequence. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. MET is a tyrosine kinase receptor, expressed in a wide variety of adult and embryonic tissues, which regulates mitogenesis, motogenesis, brain development, and dendrite and spine morphogenesis. MET, along with its ligand HGF (hepatocyte growth factor), has been implicated in diseases such as autism spectrum disorders (ASD), schizophrenia, and tumorigenesis. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 16, encoding a critical ATP-binding site, deleted in cre-expressing tissues. This deletion inactivates the intracellular tyrosine kinase domain of MET which is essential for MET function.

For example, when crossed to a strain expressing Cre recombinase in the hepatocytes (see Stock No. 003574 for example), the resulting mutant mouse strain exhibits disruption of hepatocyte survival and regeneration.

When crossed to a strain expressing Cre recombinase in cortical neurons, the resulting mutant mouse strain exhibits disrupted synaptic development and neuronal hyperconnectivity as seen in ASD.

This strain may be useful for studying neuronal growth and development in neuropsychiatric diseases such as schizophrenia and autism.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 16 and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 16 of the met proto-oncogene (Met) sequence. The construct was electroporated into 129P2/OlaHsd-derived HM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred with mice expressing EIIa-cre transgenic mice on an FVB/N background to delete the neo cassette. The resulting offspring contained multiple gene rearrangments; intact floxed-exon 16, intact floxed-neo cassette, or excision of both exon 16 and the neo cassette. Mice heterozygous for floxed exon 16 and no neo cassette were intercrossed to each other to generate the homozygous mice. These mice were maintained on a mixed FVB/129P2 background. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.

Allele

Symbol: Met^tm1Sst
Name: targeted mutation 1, Snorri S Thorgeirsson
MGI accession ID: MGI:3041135
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Met
Marker name: met proto-oncogene
Chromosome: 6
Strain of origin: 129P2/OlaHsd-Hprt^b-m3
Molecular note: Exon 16 was left flanked by single loxP sites following cre-mediated excision of floxed neo cassette from intron 16.