論文

基本情報

氏名 目加田 和之
氏名(カナ) メカダ カズユキ
氏名(英語) Mekada Kazuyuki
所属 理学部 動物学科
職名 教授
researchmap研究者コード 5000072882
researchmap機関 岡山理科大学

題名

Characterization of novel dystonia musculorum mutant mice: Implications for central nervous system abnormality.

単著・共著の別

共著

著者

M. Horie, K. Mekada, H. Sano, Y. Kikkawa, S. Chiken, T. Someya, K. Saito, M.I. Hossain, M. Nameta, K. Abe, K. Sakimura, K. Ono, A. Nambu, A. Yoshiki, H. Takebayashi

概要

We identified a novel spontaneous mutant mouse showing motor symptoms that are similar to those of the dystonia musculorum (dt) mouse. The observations suggested that the mutant mice inherited the mild dt phenotype as an autosomal recessive trait. Linkage analysis showed that the causative gene was located near D1Mit373 and D1Mit410 microsatellite markers on chromosome 1, which are close to the dystonin (Dst) gene locus. To investigate whether Dst is the causative gene of the novel mutant phenotype, we crossed the mutant with Dst gene trap (Dst(Gt)) mice. Compound heterozygotes showed a typical dt phenotype with sensory degeneration and progressive motor symptoms. DNA sequencing analysis identified a nonsense mutation within the spectrin repeats of the plakin domain. The novel mutant allele was named dt(23Rbrc). Motor abnormalities in homozygous dt(23Rbrc)/dt(23Rbrc) mice are not as severe as homozygous Dst(Gt)/Dst(Gt) mice. Histological analyses showed abnormal neurofilament (NF) accumulation in the nervous system of homozygous dt(23Rbrc)/dt(23Rbrc) mice, which is characteristic of the dt phenotype. We mapped the distribution of abnormal NF-accumulated neurons in the brain and found that they were located specifically in the brainstem, spinal cord, and in regions such as the vestibular nucleus, reticular nucleus, and red nucleus, which are implicated in posture and motor coordination pathways. The quantification of abnormal NF accumulation in the cytoplasm and spheroids (axons) of neurons showed that abnormal NF immunoreactivity was lower in homozygous dt(23Rbrc)/dt(23Rbrc) mice than in homozygous Dst(Gt)/Dst(Gt) mice. Therefore, we have identified a novel hypomorphic allele of dt, which causes histological abnormalities in the central nervous system that may account for the abnormal motor phenotype. This novel spontaneously occurring mutant may become a good model of hereditary sensory and autonomic neuropathy type 6, which is caused by mutations in the human DST gene. (C) 2016 Elsevier Inc. All rights reserved.

発表雑誌等の名称

Neurobiological of Disease

出版者

96

開始ページ

271

終了ページ

283

発行又は発表の年月

2016/12

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

ISSN

ID:DOI

ID:NAID(CiNiiのID)

ID:PMID

URL

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID