B6.129S6-Rgs13^tm1Drue/J

Stock number: 024272
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

A lacZ reporter knocks out expression of Rgs13 in this targeted mutation strain. Homozygous knockout mice show enhanced IgE-mediated mast cell degranulation and anaphylaxis.

Detailed description

Regulator of G protein signaling (RGS) family genes negatively control signaling mediated by G protein-coupled receptors (GPCRs) through GTPase-accelerating protein activity. An in-frame lacZ reporter replaces exon 4 of the Rgs13 gene in this targeted mutant strain. Homozygous knockout mice show enhanced IgE-mediated mast cell degranulation and anaphylaxis. This suggests a potential contribution to disorders of amplified mast cell activity, including idiopathic anaphylaxis. RGS13 has been found to suppress antigen-induced mast cell activation by binding the p85 subunit of PI(3)K (Pik3r1) and inhibiting protein-protein ineractions in the FcεRI (Fcer1a) signaling pathway. LacZ expression has been demonstrated in bone marrow-derived mast cells (BMMCs) and toluidine blue-positive mast cells in several organs, including skin, lung and conjuntiva. The maturation and morphology of cultured BMMCs, as well as their surface expression of FcεRI is not significantly affected.

Development

Exon 4 of the targeted gene was replaced with a lacZ-neomycin resistance cassette via homologous recombination in iTL4 129S6SvEvTac-derived embryonic stem (ES) cells. Resultant chimeric mice were backcrossed to C57BL/6J for more than 5 generations by the donating laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While one of the 27 markers throughout the genome was segregating with 129, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Rgs13^tm1Drue
Name: targeted mutation 1, Kirk M Druey
MGI accession ID: MGI:3771964
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rgs13
Marker name: regulator of G-protein signaling 13
Chromosome: 1
Strain of origin: 129S6/SvEvTac
Site of expression: LacZ is expressed in bone marrow-derived mast cells and toluidine blue-positive mast cells in several organs, including skin, lung and conjuntiva.
Molecular note: Exon 4 was replaced with a lacZ neo cassette. The absence of transcript in bone marrow-derived mast cells was confirmed by RT-PCR and the absence of protein in bone marrow-derived mast cells was confirmed by immunohistochemistry.
General note: ES cell line = iTL4 (129S6/SvEvTac)