Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice

Toshio Ohshima, Raphael Schiffmann, Gary J. Murray, Jeffrey Kopp, Jane M. Quirk, Stefanie Stahl, Chi Chao Chan, Patricia Zerfas, Jung Hwa Tao-Cheng, J. M. Ward, Roscoe O. Brady, Ashok B. Kulkarni*

*この研究の対応する著者

研究成果査読

85 被引用数 (Scopus)

抄録

Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated α-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of α-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild- type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of α-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease.

本文言語English
ページ(範囲)6423-6427
ページ数5
ジャーナルProceedings of the National Academy of Sciences of the United States of America
96
11
DOI
出版ステータスPublished - 1999 5 25
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ASJC Scopus subject areas

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