B6;129S6-Gba2^tm1Rus/J

Stock number: 018772
Research areas: Metabolism Research, Reproductive Biology Research

Description

In this strain the Gba2 gene is disrupted thereby abolishing expression. Homozygous males have impaired fertility, reduced bile acid glucosidase and glucosyltransferase activity.

Detailed description

In this strain, exons 5-10 of the glucosidase beta 2 (Gba2) gene were removed, abolishing gene expression. GBA2 is an enzyme expressed at high levels in teh testis and brain, and at lower levels in other tissues. GBA2 catalyzes the cleavage and formation of bile acid-glucose conjugates and the cleavage of glucosylceramides. Homozygotes are viable and normal in size. Homozygous males have impaired fertility due to globozoospermia, abnormal acrosomes, and highluy defective sperm mobility, while heterozygous males are fertile. Glucosylceramides accumulate in the testes to high levels.

Development

A targeting vector was designed to replace exons 5-10 of the glucosidase beta 2 (Gba2) gene with an ACN cassette. The ACN cassette, containing the neomycin resistance gene and Cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette leaving one loxP site. The construct was electroporated into 129S6/SvEvTac derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting males were bred to C57BL/6J females. These mice were maintained on a mixed C57BL/6J;129 background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Gba2^tm1Rus
Name: targeted mutation 1, David W Russell
MGI accession ID: MGI:3691302
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Gba2
Marker name: glucosidase beta 2
Chromosome: 4
Strain of origin: 129S6/SvEvTac
Molecular note: The self excising ACN cassette was inserted to replace exons 5-10 of the locus. Absence of protein was confirmed in mutant brain, testis and liver samples.