title: Myelin genes are downregulated in canine fucosidosis.
abstract: The processes regulating the complex neurodegenerative cascade of vacuolation, neuroinflammation, neuronal loss and myelin deficits in fucosidosis, a neurological lysosomal storage disorder, remain unclear. To elucidate these processes the gene expression profile of the cerebral cortex from untreated and intrathecal enzyme replacement therapy treated fucosidosis pups and age-matched unaffected controls were examined. Neuroinflammation and cell death processes were identified to have a major role in fucosidosis pathophysiology with 37% of differentially expressed (DE) genes involved in these processes. Critical, specific, early decreases in expression levels of key genes in myelin assembly were identified by gene expression profiling, including myelin-associated glycoprotein (MAG), myelin and lymphocyte protein (MAL), and oligodendrocyte myelin paranodal and inner loop protein (OPALIN). These gene expression changes may be indicative of early neuronal loss causing reduced electrical impulses required for oligodendrocyte maturation.
authors.affiliation: Teh Faculty of Veterinary Science, The UNiversity of Sydney, Camperdown NSW, 2006, Autralia. jessica.fletcher@sydney.edu.au
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Fletcher
authors.forename: Gauthami S
authors.initials: GS
authors.lastname: Kondagari
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Wright
authors.forename: Peter C
authors.initials: PC
authors.lastname: Thomson
authors.forename: Peter
authors.initials: P
authors.lastname: Williamson
authors.forename: Rosanne M
authors.initials: RM
authors.lastname: Taylor
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016923:Cell Death; D004285:Dogs; D015536:Down-Regulation; D005645:Fucosidosis / Q000503:physiopathology*; D020869:Gene Expression Profiling; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D009185:Myelin Proteins; D012333:RNA, Messenger