B6.129S1-Tgm2^tm1Rmgr/J

Stock number: 024694
Product name: Tgm2^t
Research areas: Apoptosis Research, Cell Biology Research, Developmental Biology Research, Diabetes and Obesity Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

These Tgm2^t/t floxed mice may be useful for studying the regulation of cell adhesion and protein aggregation.

Detailed description

These Tgm2^t/t floxed mice possess loxP sites flanking exons 6-8 of the transglutaminase 2, C polypeptide (Tgm2) gene. The donating investigator states that the remaining frt-flanked neo cassette conveys no abnormalities. Tgm2 is a calcium-dependent enzyme that catalyzes the crosslinking of proteins. TGM2 mediates signaling by various G-protein coupled receptors and has been found to be involved in apoptosis, fibronectin stabilization, cataract development, neurodegeneration, and wound healing. TGM2 has also been cited as an autoantigen involved in celiac disease and the onset of Type 2 diabetes mellitus (T2DM). Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 6-8 deleted in the cre-expressing tissues.

For example, when bred to mice carrying the Tg(CMV-cre)1Cgn allele ( see Stock No. 006054), mice exhibit normal glucose tolerance, insulin sensitivity and glucose stimulated insulin secretion on a standard or high fat diet. Fibroblasts from these mice exhibit decreased adhesion. When these TGM2-deficient mice are bred to B6CBA-Tg(HDexon1)62Gpb/1J mice (Stock No. 002810), resulting offspring contain more huntingtin protein aggregates within the cerebral cortex and striatum, with no difference in the onset of motor dysfunction and the mean lifespan, compared to Tg(HDexon1)62Gpb transgenic mice.

Development

A targeting vector was designed to insert a loxP site and a frt-flanked neomycin resistance (neo) cassette upstream of exon 6, and a second loxP site downstream of exon 8 of transglutaminase 2, C polypeptide (Tgm2) gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice. These mice were bred to C57BL/6J mice for at least 12 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tgm2^tm1Rmgr
Name: targeted mutation 1, Robert M Graham
MGI accession ID: MGI:3525256
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Tgm2
Marker name: transglutaminase 2, C polypeptide
Chromosome: 2
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: LoxP sites that flank exons 6-8 were inserted by homologous recombination.