B6.129-Ryr2^tm1Krbr/JnsnJ

Stock number: 026628
Product name: Ryr2 flox
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

Ryr2^flox/flox mice may be useful for studying cardiac dysfunction during heart failure.

Detailed description

Ryr2^flox/flox mice possess a loxP sites flanking a neo cassette and exon 20 (ENSMUSE00000618658) of the ryanodine receptor 2, cardiac (Ryr2) gene (Ryr2-201, Transcript ID ENSMUST00000021750.15) . RYR2 is major Ca²⁺ release channel involved in excitation-contraction coupling in the beating heart. Homozygous mice are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 3 deleted in the cre-expressing tissue.

For example when bred to B6.FVB(129)-Tg(Myh6-cre/Esr1*)1Jmk/J mice (Stock No. 005657) expressing tamoxifen-inducible Cre recombinase (MerCreMer), resulting offspring exhibit functional and structural hallmarks of heart failure, including bradycardia, arrhythmia, and sudden cardiac death as soon as 4 days after initial tamoxifen administration.

Previously, it was reported that exon 3 was floxed in this strain. More recent data has now suggested that exon 20 is floxed.

Development

A targeting vector was designed to insert a loxP site followed by a neomycin resistance (neo) cassette upstream of exon 20 (ENSMUSE00000618658) and a single loxP site downstream of exon 20 of the ryanodine receptor 2, cardiac (Ryr2) gene (Ryr2-201, Transcript ID ENSMUST00000021750.15). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6J to establish a colony. Ryr2^flox/flox mice were bred to C57BL/6J mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Previously, it was reported that exon 3 was floxed in this strain. More recent data has now suggested that exon 20 is floxed.

Allele

Symbol: Ryr2^tm1Krbr
Name: targeted mutation 1, Kenneth R Boheler
MGI accession ID: MGI:5576915
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Ryr2^flox
Marker symbol: Ryr2
Marker name: ryanodine receptor 2, cardiac
Marker synonyms: 9330127I20Rik; ARVC2; ARVD2; RyR; RYR-2; VACRDS; VTSIP
Chromosome: 13
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neomycin resistance cassette with a 5' loxP site was inserted upstream of exon 20. An additional loxP site was inserted downstream of exon 20. Previously, it was reported that exon 3 was floxed in this strain. More recent data has now suggested that exon 20 is floxed.