title: Identification of new markers for neurodegeneration process in the mouse model of Sly disease as revealed by expression profiling of selected genes.
abstract: Sly disease (MPS VII) is an autosomal-recessive lysosomal storage disorder resulting from beta-glucuronidase deficiency, which is characterized by a severe neurological impairment. MPS VII mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, thus appearing to be an excellent tool to delineate disease pathogenesis. The relationship between abnormal glycosaminoglycan storage and neurodysfunction is not yet well understood, but inflammatory components can be involved, as in several neurological lysosomal disorders. Inflammatory biomarkers are thus good candidates to evaluate the neurodegeneration state of the disease. By using quantitative polymerase chain reaction, we have compared the expression of selected genes of normal and MPS VII cerebral tissues, focusing on inflammation and apoptosis-related genes. The gene expression was evaluated in various brain regions throughout the lifetime of the animals. We have identified a specific expression profile for 27 genes, which was strongly marked in the central nervous system posterior region. Finally, new Sly disease markers were characterized that reflect neurological deterioration state, and that can be used in preclinical follow-up studies.
authors.affiliation: Inserm U640, CNRS UMR 8151, Université Paris Descartes, Chemical and Genetic Pharmaceutical Laboratory, Ecole Nationale Supérieure de Chimie de Paris, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Richard
authors.forename: Audrey
authors.initials: A
authors.lastname: Arfi
authors.forename: Hervé
authors.initials: H
authors.lastname: Rhinn
authors.forename: Christelle
authors.initials: C
authors.lastname: Gandolphe
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis*; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D016538:Mucopolysaccharidosis VII / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers