title: Primary culture of neural cells isolated from the cerebellum of newborn and adult mucopolysaccharidosis type IIIA mice.
abstract: In order to evaluate the mechanisms leading to neuropathology in Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo syndrome), we have harvested and cultured primary neural cells isolated from the cerebellum of newborn and adult MPS-IIIA and unaffected mice. Cell viability and plating efficiency were comparable for brain tissue obtained from either newborn or adult MPS-IIIA and unaffected mice. Cultures (newborn and adult) comprised a mixed brain cell population including astrocytes, oligodendrocytes, and neurons. Newborn MPS-IIIA cells contained inclusions and vacuoles consistent with the pathology present in affected brain tissue. Newborn and adult MPS-IIIA brain cells had approximately 5-7% of the sulfamidase activity present in primary neural cells cultured from unaffected newborn and adult mice. In addition, high levels of glucosamine-N-sulfate[alpha-1,4]hexuronic acid, a heparan sulfate-derived disaccharide, were detected in both newborn and adult MPS-IIIA brain cells. These results suggest that the primary MPS-IIIA brain cells exhibit characteristics of MPS-IIIA phenotype at the histopathological and biochemical level in culture.
authors.affiliation: Department of Genetic Medicine, Lysosomal Diseases Research Unit, Children, Youth and Women's Health Service, 72 King William Road, North Adelaide, SA 5006, Australia. leanne.sutherland@adelaide.edu.au
authors.forename: L M
authors.initials: LM
authors.lastname: Sutherland
authors.forename: K M
authors.initials: KM
authors.lastname: Hemsley
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004187:Disaccharides / Q000378:metabolism; D004195:Disease Models, Animal; D006603:Hexuronic Acids / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009084:Mucopolysaccharidosis III / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D014617:Vacuoles / Q000378:metabolism / Q000473:pathology
chemical_list: D004187:Disaccharides; D006603:Hexuronic Acids; D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase