Mutation of beta-glucosidase 2 causes glycolipid storage disease and impaired male fertility.
J Clin Invest
; 116(11): 2985-94, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-17080196
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicolipídeos
/
Beta-Glucosidase
/
Infertilidade Masculina
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Doenças Metabólicas
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos