B6N;129-Lrba^{Gt(OST69142)Lex}/WgkJ

Stock number: 030043
Product name: LRBA KO
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

LRBA^-/- mice are useful when studying resistance to acute graft vs host disease (GvHD).

Detailed description

LRBA^-/- mice have a possess β-geo cassette followed by a polyadenylation signal inserted between exons 2 and 3 of the LPS-responsive beige-like anchor (Lrba) gene. LRBA encodes a scaffolding protein that is a member of the PH-BEACH-WD40 (PBW) protein family involved in cell-cell and protein-protein interactions as well as in vesicle trafficking. Mice that are homozygous for this allele are viable and fertile. LRBA^-/- mice show resistance to acute graft vs host disease (GvHD). They exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Natural Killer (NK) cells from these mice exhibit impaired signaling by the key NK activating receptors, such as NKp46 and NKG2D. Induction of IFN-γ by cytokines remains intact.

Development

A gene trap targeting vector was used replace the endogenous LPS-responsive beige-like anchor (Lrba) gene with a splice acceptor sequence (SA) followed by a β-geo selection cassette (a fusion between a β-galactosidase and neomycin resistance genes) followed by a polyadenylation signal. This gene trap targeting vector integrated into the intron between exons 2 and 3, via electroporation into 129S5/SvEvBrd-derived Lex-1 embryonic stem (ES) cells. These OST69142 ES cells were injected into blastocysts. The resulting chimeric mice were bred with 129Sv mice and were subsequently backcrossed to C57BL/6NTac for at least 6 generations by the donating lab (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. Four of the 43 markers throughout the genome were segregating, suggesting ain incomplete backcross.

Allele

Symbol: Lrba^{Gt(OST69142)Lex}
Name: gene trap OST69142, Lexicon Genetics
MGI accession ID: MGI:4173110
Generation method: Gene trapped
Attributes: Null/Knockout
Synonyms: LRBA^-
Marker symbol: Lrba
Marker name: LPS-responsive beige-like anchor
Marker synonyms: BGL; CDC4L; CVID8; D3Ertd775e; LAB300; Lba; uc.147
Chromosome: 3
Strain of origin: 129S5/SvEvBrd
Molecular note: The gene trap targeting vector (consisting of a splice acceptor sequence (SA) followed by a beta-geo selection cassette and a polyadenylation signal) integrated into the intron between exons 2 and 3. Northern blot of kidney and brain confirmed that homozygous mice lack detectable mRNA.