title: Perturbation of myelin basic protein (Mbp) splice variant expression in developing rat cerebellum following perinatal exposure to methylmercury.
abstract: Myelin sheaths surrounding axons are essential for saltatory conduction of nerve impulse in the central nervous system. A major protein constituent of myelin sheaths is produced by the myelin basic protein (Mbp) gene, whose expression in oligodendrocytes is conserved across vertebrates. In rat, five Mbp splice variants resulting from alternative splicing of exons 2, 5 and/or 6 are characterized. We developed a PCR-based strategy to quantify individual Mbp splice variants and characterized a sixth Mbp splice variant lacking only exon 5. This newly identified splice variant is predominantly expressed in developing rat brain and has orthologs in mouse and human. Many neurotoxic chemicals can perturb myelination and Mbp gene expression. Regulation of Mbp gene expression at the post-transcriptional level was assessed following perinatal exposure to neurotoxic methylmercury (2 mg/kg b.w./day). Similar reductions in total and individual Mbp splice variant mRNA levels suggest that methylmercury-induced perturbation in Mbp gene expression occurred as a consequence of decreased oligodendrocyte cell population in absence of a significant impact on its post-transcriptional regulation.
authors: Hazard Identification Division, HECSB, Health Canada, Tunney's Pasture, Ottawa, ON, K1A 0L2, Canada.
authors: Bhaja K
authors: BK
authors: Padhi
authors: Guillaume
authors: G
authors: Pelletier
mesh_terms: D000367:Age Factors; D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015536:Down-Regulation; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D008767:Methylmercury Compounds / Q000633:toxicity*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C436006:Mbp protein, rat; D008767:Methylmercury Compounds; D004676:Myelin Basic Protein; D020033:Protein Isoforms; D012333:RNA, Messenger