STOCK Jup^tm1.1Glr/J

Stock number: 017575
Research areas: Apoptosis Research, Cell Biology Research, Developmental Biology Research, Research Tools

Description

These PG^flox mutant mice possess loxP sites flanking exon 1 of the junction plakoglobin (Jup) gene. This strain may be useful for studying plakoglobin in the assembly of adherens junctions and desmosomes, and in the regulation of Wnt/β-catenin signalling.

Detailed description

These PG^flox mutant mice possess loxP sites flanking exon 1 of the junction plakoglobin (Jup) gene. PG is a member of the armadillo protein family found in submembranous plaques of desmosomes and adherens junctions where it directly interacts with cadherins. Mutations in PG have been found in cases of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues. For example, when bred to mice carrying the Tg(Myh6-cre/Esr1*)1Jmk transgene (see Stock No. 005657), PG deletion in the adult myocardium after tamoxifen induction results in progressive loss of cardiac myocytes, extensive inflammatory infiltration, fibrous tissue replacement, and cardiac dysfunction similar to those of ARVC patients. This strain may be useful for studying plakoglobin in the assembly of adherens junctions and desmosomes, and in the regulation of Wnt/β-catenin signalling.

Development

A targeting vector was designed to insert a loxP site upstream of exon 1, followed by a second loxP site and a frt-flanked neomycin resistance (neo) cassette downstream of exon 1 of the junction plakoglobin (Jup) gene. The construct was electroporated into 129S6/SvEvTac-derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred. Offspring were bred with mice carrying the Tg(ACTFLPe)9205Dym transgene to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. These PG^flox mice were maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Jup^tm1.1Glr
Name: targeted mutation 1.1, Glenn L Radice
MGI accession ID: MGI:4947239
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Jup
Marker name: junction plakoglobin
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site was inserted upstream of exon 1, and a loxP site and an FRT-flanked neo cassette were introduced into intron 1 via homologous recombination. Flp mediated recombination removed the neo cassette leaving exon 1 floxed.