title: The VF rat with abnormal myelinogenesis has a mutation in Dopey1.
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.
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka, 598-8531, Japan.
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D018389:Codon, Nonsense; D006056:Golgi Apparatus / Q000473:pathology / Q000502:physiology; D066128:Gray Matter / Q000473:pathology / Q000503:physiopathology; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics* / Q000473:pathology / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D014202:Tremor / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D014617:Vacuoles / Q000235:genetics / Q000473:pathology / Q000502:physiology; D066127:White Matter / Q000473:pathology / Q000503:physiopathology
chemical_list: D018389:Codon, Nonsense; C000595895:Dop1a protein, rat; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: hypomyelination; myelin traffic; myelin vacuole; oligodendrocyte