RRC ID 33270
著者 Tanaka M, Izawa T, Yamate J, Franklin RJ, Kuramoto T, Serikawa T, Kuwamura M.
タイトル The VF rat with abnormal myelinogenesis has a mutation in Dopey1.
ジャーナル Glia
Abstract The vacuole formation (VF) rat is an autosomal recessive myelin mutant characterized by generalized tremor, hypomyelination, and periaxonal vacuole formation of the central nervous system (CNS). Here, we report the most likely causative gene for neurological disease in the VF rat and pursue its roles in the development and maintenance of the CNS myelin. We identified a nonsense mutation in the dopey family member 1 (Dopey1) located on rat chromosome 8. Expression level of Dopey1 mRNA was decreased and DOPEY1 protein was undetectable both in the white and gray matter of the spinal cords in the VF rats. Double immunohistochemistry demonstrated that DOPEY1 was mainly expressed in neurons and oligodendrocytes in the wild-type rats, whereas no positive cells were detected in the VF rats. We also demonstrated a marked reduction in myelin components both at mRNA and protein levels during myelinogenesis in the VF rats. In addition, proteolipid protein and myelin-associated glycoprotein accumulated in oligodendrocyte cell body, suggesting that Dopey1 is likely to be involved in the traffic of myelin components. Our results highlighted the importance of Dopey1 for the development and maintenance of the CNS myelin.
巻・号 62(9)
ページ 1530-42
公開日 2014-9-1
DOI 10.1002/glia.22698
PMID 24863653
MeSH Animals Central Nervous System Diseases / genetics* Central Nervous System Diseases / pathology Central Nervous System Diseases / physiopathology* Codon, Nonsense Golgi Apparatus / pathology Golgi Apparatus / physiology Gray Matter / pathology Gray Matter / physiopathology Myelin Proteolipid Protein / metabolism Myelin Sheath / genetics* Myelin Sheath / pathology Myelin Sheath / physiology* Myelin-Associated Glycoprotein / metabolism Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism* Neurons / pathology Neurons / physiology Oligodendroglia / pathology Oligodendroglia / physiology RNA, Messenger / metabolism Rats Spinal Cord / pathology Spinal Cord / physiopathology Tremor / genetics Tremor / pathology Tremor / physiopathology Vacuoles / genetics Vacuoles / pathology Vacuoles / physiology White Matter / pathology White Matter / physiopathology
IF 5.984
引用数 6
WOS 分野 NEUROSCIENCES
リソース情報
ラット VF/Kyo(strainID=21)