title: Systemic inflammation in glucocerebrosidase-deficient mice with minimal glucosylceramide storage.
abstract: Gaucher disease, the most common lysosomal storage disease, is caused by a deficiency of glucocerebrosidase resulting in the impairment of glucosylceramide degradation. The hallmark of the disease is the presence of the Gaucher cell, a macrophage containing much of the stored glucosylceramide found in tissues, which is believed to cause many of the clinical manifestations of the disease. We have developed adult mice carrying the Gaucher disease L444P point mutation in the glucocerebrosidase (Gba) gene and exhibiting a partial enzyme deficiency. The mutant mice demonstrate multisystem inflammation, including evidence of B cell hyperproliferation, an aspect of the disease found in some patients. However, the mutant mice do not accumulate large amounts of glucosylceramide or exhibit classic Gaucher cells in tissues.
authors: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Hiroki
authors: H
authors: Mizukami
authors: Yide
authors: Y
authors: Mi
authors: Ryuichi
authors: R
authors: Wada
authors: Mari
authors: M
authors: Kono
authors: Tadashi
authors: T
authors: Yamashita
authors: Yujing
authors: Y
authors: Liu
authors: Norbert
authors: N
authors: Werth
authors: Roger
authors: R
authors: Sandhoff
authors: Konrad
authors: K
authors: Sandhoff
authors: Richard L
authors: RL
authors: Proia
mesh_terms: D000818:Animals; D005776:Gaucher Disease / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D005962:Glucosylceramidase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012867:Skin / Q000473:pathology
chemical_list: D005963:Glucosylceramides; D005962:Glucosylceramidase