B6.129S7(SJL)-Cracr2a^tm1.1Ygwa/J

Stock number: 036233
Product name: CRACR2A^fl
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

CRACR2A^fl/fl mice have loxP sites flanking exons 3-4 of the Cracr2a gene. These mice are useful for studying the role of subsynaptic vesicles in mediating the signaling pathways required for T cell activation.

Detailed description

CRACR2A^fl/fl mice have loxP sites flanking exons 3-4 of the calcium release activated channel regulator 2A (Cracr2a) gene. Cracr2a encodes a lymphocyte-specific large Rab GTPase that acts as a cytoplasmic calcium-sensor in T cells by regulating CRAC channel activation in response to T cell receptor (TCR) stimulation. CRACR2A-mediated signaling has been implicated in Th1 cell differentiation and mutations in CRACR2A have been associated with Parkinson disease, nonalcoholic fatty liver disease, atrial fibrillation, and chronic infection of HIV type 1.

Homozygous mice are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-4 deleted in Cre-expressing tissues. Aberrant splicing from exon 2 to exon 5 results in frameshift and early termination.

When bred to Cd4-Cre mice (Stock No. 022071) to delete Cracr2a in T cells, resulting mice have lower Th1 responses as judged using acute LCMV (lymphocytic choriomeningitis virus) infection and an animal models of of multiple sclerosis (experimental autoimmune encephalomyelitis).

Development

The CRACR2A^fl targeting vector was designed to insert loxP sites flanking exons 3-4 of the calcium release activated channel regulator 2A (Cracr2a) gene. A third loxP site and a frt-flanked neomycin resistance (neo) cassette were inserted upstream of exon 3. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to ACTB:FLPe B6J mice (Stock No. 005703) to remove the neo cassette. Progeny were crossed to remove the FLP-expressing transgene. Resulting CRACR2A^fl/fl mice were bred to C57BL/6J mice (Stock No. 000664) for at least 10 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Cracr2a^tm1.1Ygwa
Name: targeted mutation 1.1, Yousang Gwack
MGI accession ID: MGI:6343391
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: CRACR2A^fl
Marker symbol: Cracr2a
Marker name: calcium release activated channel regulator 2A
Marker synonyms: Efcab4b; LOC243645; LOC381812; RAB46; RGD1563719
Chromosome: 6
Strain of origin: 129S7/SvEvBrd-Hprt1^b-m2
Molecular note: Exons 3 and 4 are flanked by loxP sites.