title: Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible.
abstract: The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the cellular and molecular mechanisms that underlie brain dysfunction. In the mouse model of mucopolysaccharidosis VII, we found that specific regions of the brain are vulnerable to neurodegeneration, characterized by the presence of ubiquitin inclusions, neurofilament inclusions, and reactive astrogliosis. The pathological lesions were found predominantly in the hippocampus and cerebral cortex, and they increased progressively with age. Treatment with a recombinant viral vector to correct the enzymatic defect quantitatively reversed the neurodegenerative lesions in targeted regions to normal levels.
authors.affiliation: Department of Pathobiology and Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Heuer
authors.forename: Marco A
authors.initials: MA
authors.lastname: Passini
authors.forename: Kanli
authors.initials: K
authors.lastname: Jiang
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parente
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: John H
authors.initials: JH
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D018450:Disease Progression; D005822:Genetic Vectors / Q000494:pharmacology / Q000627:therapeutic use; D002479:Inclusion Bodies / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016538:Mucopolysaccharidosis VII / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D025801:Ubiquitin / Q000032:analysis; D014614:Vaccines, Synthetic / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D025801:Ubiquitin; D014614:Vaccines, Synthetic