Mutations in human GBA (glucosidase, beta, acid) can cause Gaucher disease, an autosomal recessive lysosomal (lipid) storage disease, and have been associated with late onset Parkinson's disease and Lewy body dementia. These mice express the mutant D427V Gba protein, which corresponds to the D409V mutation in the mature human GBA protein, and possess loxP sites flanking exons 6 through 8. Mice that are heterozygous for the targeted mutation are viable and fertile. Homozygous Gba D409V knock-in mice show a significant reduction in Gba protein level and glucocerebrosidase activity, and a significant increase in glucosylsphingosine in both brain and liver tissues.
Heterozygotes demonstrate significant cognitive impairment by the age of 12 months, as determined by both Morris water maze and Y-maze behavioral tests (PMID: 31299418).
When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 6 through 8 deleted in the cre-expressing tissues and will no longer express the mutant D427V protein.
Preliminary characterization was presented in a poster at the 2015 Society for Neuroscience conference.
