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- Title
Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility.
- Authors
Yildiz, Yildiz; Matern, Heidrun; Thompson, Bonne; Allegood, Jeremy C; Warren, Rebekkah L; Ramirez, Denise M O; Hammer, Robert E; Hamra, F Kent; Matern, Siegfried; Russell, David W
- Abstract
beta-Glucosidase 2 (GBA2) is a resident enzyme of the endoplasmic reticulum thought to play a role in the metabolism of bile acid-glucose conjugates. To gain insight into the biological function of this enzyme and its substrates, we generated mice deficient in GBA2 and found that these animals had normal bile acid metabolism. Knockout males exhibited impaired fertility. Microscopic examination of sperm revealed large round heads (globozoospermia), abnormal acrosomes, and defective mobility. Glycolipids, identified as glucosylceramides by mass spectrometry, accumulated in the testes, brains, and livers of the knockout mice but did not cause obvious neurological symptoms, organomegaly, or a reduction in lifespan. Recombinant GBA2 hydrolyzed glucosylceramide to glucose and ceramide; the same reaction catalyzed by the beta-glucosidase acid 1 (GBA1) defective in subjects with the Gaucher's form of lysosomal storage disease. We conclude that GBA2 is a glucosylceramidase whose loss causes accumulation of glycolipids and an endoplasmic reticulum storage disease.
- Subjects
LIPID metabolism; ANIMAL experimentation; COMPARATIVE studies; FERTILIZATION in vitro; GENE expression; GLYCOSIDASES; GLYCOSYLATION; IMMUNITY; INFERTILITY; RESEARCH methodology; MEDICAL cooperation; METABOLIC disorders; MICE; GENETIC mutation; RESEARCH; RESEARCH funding; SPERM motility; TESTIS; EVALUATION research; SPERM count
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 11, p2985
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/jci29224