title: Glycosaminoglycan storage in cultured neonatal murine mucopolysaccharidosis type VII neuroglial cells and correction by beta-glucuronidase gene transfer.
abstract: The inherited deficiency of beta-glucuronidase activity causes the lysosomal storage disorder mucopolysaccharidosis (MPS) type VII (Sly disease). The sequential catabolism of glycosaminoglycans in lysosomes is blocked, and undegraded substrates accumulate in cells of many tissues, including neurons and glia in the brain. To evaluate the deficient metabolic pathway, primary cultures of mixed brain cells were established from newborn MPS VII mice. beta-Glucuronidase levels and glycosaminoglycan accumulation were studied in normal, carrier, and MPS VII cells. Retroviral vector-mediated transfer of a normal beta-glucuronidase cDNA corrected the enzymatic deficiency in MPS VII cells and restored glycosaminoglycan catabolism to normal. High levels of beta-glucuronidase expression were sustained in vector-corrected nondividing glial cell cultures for >2 months. These studies provide an in vitro model for evaluating somatic gene transfer in neural cells affected in mucopolysaccharidoses.
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, U.S.A.
authors.forename: R M
authors.initials: RM
authors.lastname: Taylor
authors.forename: J H
authors.initials: JH
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006579:Heterozygote; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D016538:Mucopolysaccharidosis VII / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D005966:Glucuronidase