Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts.
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| Abstract |
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.
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| Authors | P L Chang, R G Davidson |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 77 Issue 10 Pg. 6166-70 (Oct 1980) ISSN: 0027-8424 [Print] United States |
| PMID | 6108562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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