文章基本信息

标题：Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts
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作者：P L Chang ; R G Davidson
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1980
卷号：77
期号：10
页码：6166-6170
DOI：10.1073/pnas.77.10.6166
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Metachromatic leukodystrophy and multiple sulfatase deficiency disorder are severe neurodegenerative diseases inherited as separate autosomal recessive traits. Arylsulfatase A (aryl-sulfate sulfohydrolase, EC 3.1.6.1 ) activity is deficient in both diseases but in multiple sulfatase deficiency disorder, activities of arylsulfatases B and C and other sulfatases are also reported to be reduced. Somatic hybrid cell clones produced by fusing cultured fibroblasts from patients with these diseases were isolated by a nonselective technique based on unit-gravity sedimentation. Arylsulfatase A activity was restored in these hybrids. The complemented enzyme resembled the normal arylsulfatase A in heat stability, pH optimum, Km, electrophoretic mobility, and immunologic reactivity. Because a structurally normal enzyme can be restored in a hybrid only though intergenic complementation, these results indicate that the mutations responsible for the deficiency of arylsulfatase A activity in metachromatic leukodystrophy and multiple sulfatase deficiency disorder are nonallelic and that at least two genetic loci control the expression of arylsulfatase A activity in the human genome. Furthermore, arylsulfatase C activity was also restored to normal in the hybrids, indicating that a common sulfatase inhibitor is not the cause of the multiple sulfatse deficiency.