Abstract
Multiple sulfatase deficiency (MSD) is an inherited disorder characterized by deficient activity of seven different sulfatases. Genetic complementation for steroid sulfatase (STS), arylsulfatase A, and N-acetylgalactosamine 6-SO4 sulfatase was demonstrated in somatic cell hybrids between MSD fibroblasts and mouse cells ( LA9 ) or Chinese hamster cells ( CHW ). In an electrophoretic system that separates human and rodent STS isozymes, enzyme from hybrids migrated as human enzyme. We concluded that the rodent cell complemented the MSD deficiency and allowed normal expression of the STS structural gene. Some MSD- LA9 hybrids showed significant levels of human arylsulfatase A activity, as shown by the immunoprecipitation of active enzyme by human-specific antiserum. Complementation was also suggested for N-acetylgalactosamine 6- sulfatate sulfatase (GalNAc-6S sulfatase) in several MSD- LA9 hybrids by the demonstration of a significant increase in activity (10-fold) over that of the GalNAc-6S sulfatase-deficient parental mouse and MSD cells. Thus, it was possible to demonstrate complementation for more than one sulfatase in a single MSD-rodent hybrid. Normal levels of sulfatase activity in hybrids indicate that the sulfatase structural genes are intact in MSD cells.
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- Austin J. H. Studies in metachromatic leukodystrophy. XII. Multiple sulfatase deficiency. Arch Neurol. 1973 Apr;28(4):258–264. doi: 10.1001/archneur.1973.00490220066010. [DOI] [PubMed] [Google Scholar]
- BAUM H., DODGSON K. S., SPENCER B. The assay of arylsulphatases A and B in human urine. Clin Chim Acta. 1959 May;4(3):453–455. doi: 10.1016/0009-8981(59)90119-6. [DOI] [PubMed] [Google Scholar]
- Basner R., von Figura K., Glössl J., Klein U., Kresse H., Mlekusch W. Multiple deficiency of mucopolysaccharide sulfatases in mucosulfatidosis. Pediatr Res. 1979 Dec;13(12):1316–1318. doi: 10.1203/00006450-197912000-00002. [DOI] [PubMed] [Google Scholar]
- Bruns G. A., Mintz B. J., Leary A. C., Regina V. M., Gerald P. S. Human lysosomal genes: arylsulfatase A and beta-galactosidase. Biochem Genet. 1979 Dec;17(11-12):1031–1059. doi: 10.1007/BF00504344. [DOI] [PubMed] [Google Scholar]
- Chang P. L., Davidson R. G. Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6166–6170. doi: 10.1073/pnas.77.10.6166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang P. L., Rosa N. E., Davidson R. G. Differential assay of arylsulfatase A and B activities: a sensitive method for cultured human cells. Anal Biochem. 1981 Nov 1;117(2):382–389. doi: 10.1016/0003-2697(81)90795-8. [DOI] [PubMed] [Google Scholar]
- Corsaro C. M., Migeon B. R. Effect of intercellular communication on the selection of intraspecific human hybrids in HAT and ouabain. Somatic Cell Genet. 1978 Sep;4(5):541–551. doi: 10.1007/BF01542925. [DOI] [PubMed] [Google Scholar]
- D'Azzo A., Hoogeveen A., Reuser A. J., Robinson D., Galjaard H. Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4535–4539. doi: 10.1073/pnas.79.15.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davidson R. L., Gerald P. S. Improved techniques for the induction of mammalian cell hybridization by polyethylene glycol. Somatic Cell Genet. 1976 Mar;2(2):165–176. doi: 10.1007/BF01542629. [DOI] [PubMed] [Google Scholar]
- Eisenberg L. R., Migeon B. R. Enrichment of human heterokaryons by Ficoll gradient for complementation analysis of iduronate sulfatase deficiency. Somatic Cell Genet. 1979 Nov;5(6):1079–1089. doi: 10.1007/BF01542661. [DOI] [PubMed] [Google Scholar]
- Eto Y., Wiesmann U. N., Carson J. H., Herschkowitz N. N. Multiple sulfatase deficiencies in cultured skin fibroblasts. Occurrence in patients with a variant form of metachromatic leukodystrophy. Arch Neurol. 1974 Feb;30(2):153–156. doi: 10.1001/archneur.1974.00490320041005. [DOI] [PubMed] [Google Scholar]
- Farooqui A. A. Effect of neuraminidase on the multiple forms of arylsulphatase B. Biochimie. 1976;58(6):759–761. doi: 10.1016/s0300-9084(76)80405-1. [DOI] [PubMed] [Google Scholar]
- Fiddler M. B., Vine D., Shapira E., Nadler H. L. Is multiple sulphatase deficiency due to defective regulation of sulphohydrolase expression? Nature. 1979 Nov 1;282(5734):98–100. doi: 10.1038/282098a0. [DOI] [PubMed] [Google Scholar]
- Fluharty A. L., Stevens R. L., Davis L. L., Shapiro L. J., Kihara H. Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts. Am J Hum Genet. 1978 May;30(3):249–255. [PMC free article] [PubMed] [Google Scholar]
- Hall C. W., Liebaers I., Di Natale P., Neufeld E. F. Enzymic diagnosis of the genetic mucopolysaccharide storage disorders. Methods Enzymol. 1978;50:439–456. doi: 10.1016/0076-6879(78)50048-7. [DOI] [PubMed] [Google Scholar]
- Horwitz A. L. Genetic complementation studies of multiple sulfatase deficiency. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6496–6499. doi: 10.1073/pnas.76.12.6496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kresse H., Holtfrerich D. Thiosulfate-mediated increase of arylsulfatase activities in multiple sulfatase deficiency disorder fibroblasts. Biochem Biophys Res Commun. 1980 Nov 17;97(1):41–48. doi: 10.1016/s0006-291x(80)80131-8. [DOI] [PubMed] [Google Scholar]
- Kucherlapati R. S., Baker R. M., Ruddle F. H. Ouabain as a selective agent in the isolation of somatic cell hybrids. Birth Defects Orig Artic Ser. 1975;11(3):192–193. [PubMed] [Google Scholar]
- March S. C., Parikh I., Cuatrecasas P. A simplified method for cyanogen bromide activation of agarose for affinity chromatography. Anal Biochem. 1974 Jul;60(1):149–152. doi: 10.1016/0003-2697(74)90139-0. [DOI] [PubMed] [Google Scholar]
- Meyers M. B., van Diggelen O. P., van Diggelen M., Shin S. Isolation of somatic cell mutants with specified alterations in hypoxanthine phosphoribosyltransferase. Somatic Cell Genet. 1980 Mar;6(2):299–306. doi: 10.1007/BF01538803. [DOI] [PubMed] [Google Scholar]
- Mohandas T., Shapiro L. J., Sparkes R. S., Sparkes M. C. Regional assignment of the steroid sulfatase-X-linked ichthyosis locus: implications for a noninactivated region on the short arm of human X chromosome. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5779–5783. doi: 10.1073/pnas.76.11.5779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohandas T., Sparkes R. S., Hellkuhl B., Grzeschik K. H., Shapiro L. J. Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6759–6763. doi: 10.1073/pnas.77.11.6759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapira E., DeGregorio R. R., Nadler H. L. Immunologic studies of arylsulfatase A in normal and metachromatic leukodystrophy liver. Pediatr Res. 1978 Mar;12(3):199–203. doi: 10.1203/00006450-197803000-00007. [DOI] [PubMed] [Google Scholar]
- Shapira E., Nadler H. L. The nature of the residual arylsulfatase activity in metachromatic leukodystrophy. J Pediatr. 1975 Jun;86(6):881–884. doi: 10.1016/s0022-3476(75)80218-6. [DOI] [PubMed] [Google Scholar]
- Suzuki Y., Sakuraba H., Hayashi K., Suzuki K., Imahori K. Beta-galactosidase-neuraminidase deficiency: restoration of beta-galactosidase activity by protease inhibitors. J Biochem. 1981 Jul;90(1):271–273. doi: 10.1093/oxfordjournals.jbchem.a133462. [DOI] [PubMed] [Google Scholar]
- Waheed A., Hasilik A., von Figura K. Enhanced breakdown of arylsulfatase A in multiple sulfatase deficiency. Eur J Biochem. 1982 Apr 1;123(2):317–321. doi: 10.1111/j.1432-1033.1982.tb19770.x. [DOI] [PubMed] [Google Scholar]
- Yutaka T., Okada S., Kato T., Inui K., Yabuuchi H. Properties of sulfatases in cultured skin fibroblasts of multiple sulfatase deficient patients. Clin Genet. 1981 Oct;20(4):296–303. doi: 10.1111/j.1399-0004.1981.tb01036.x. [DOI] [PubMed] [Google Scholar]

