B6.129X1(C)-Gpr132^tm1Witt/J

Stock number: 008576
Research areas: Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs

Description

Mice homozygous for this G protein-coupled receptor 132 (Gpr132, G2A) targeted mutation demonstrate a normal pattern of T and B lineage differentiation through young adulthood when they are indistinguishable from wild-type littermates. As they age, they develop secondary lymphoid organ enlargement associated with abnormal expansion of both T and B lymphocytes. Homozygotes greater than one year old develop a slowly progressive wasting syndrome, characterized by lymphocytic infiltration into various tissues, glomerular immune complex deposition, and anti-nuclear autoantibodies. This strain represents a novel model of late-onset autoimmune syndrome.

Detailed description

Mice homozygous for this targeted mutation demonstrate a normal pattern of T and B lineage differentiation through young adulthood when they are indistinguishable from wildtype littermates. As they age, they develop secondary lymphoid organ enlargement associated with abnormal expansion of both T and B lymphocytes. Homozygotes greater than one year old develop a slowly progressive wasting syndrome, characterized by lymphocytic infiltration into various tissues, glomerular immune complex deposition, and anti-nuclear autoantibodies. T cells are hyperresponsive to TCR stimulation, exhibiting enhanced proliferation and a lower threshold of activation. RT-PCR analysis of RNA from homozygous pre-B and T cells does not detect mRNA. The lacZ marker incorporated in the targeted mutation is expressed in lymphoid tissues like bone marrow, spleen and thymus. Expression of lacZ in the testis (primarily mature spermatids) and the cortical-medullary junction of the kidney have also been observed. Low levels of lacZ expression are seen in lymphoid organs of heterozygotes. This strain represents a novel model of late-onset autoimmune syndrome.

Development

A targeting vector was constructed to replace the second exon with an IRES beta galactosidase (LacZ) ane PGK-neomycin resistance cassette. The vector was electroporated into 129X1/SvJ-derived embryonic stem cells. Appropriately-targeted cells were injected into C57BL/6 blastocysts. Chimeric males were crossed with BALB/c females, then backcrossed to C57BL/6 for 12 generations.

Genetic assessment carried out in January of 2022 demonstrated that this strain is segregating for both the Cd45.1 (Ptprc^a) and Cd45.2 (Ptprc^b) alleles.

Allele

Symbol: Gpr132^tm1Witt
Name: targeted mutation 1, Owen N Witte
MGI accession ID: MGI:2388138
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Gpr132
Marker name: G protein-coupled receptor 132
Chromosome: 12
Strain of origin: 129X1/SvJ
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: The gene was disrupted by replacement of exon 2 (98% of the total coding sequence) with an IRES-lacZ-PGK-neo cassette. Absence of gene expression was confirmed by RT-PCR analysis of pre-B and -T cells from homozygous mutant animals.