Establishment and pathological analyses of transgenic marmoset models of polyglutamine diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670446
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: NAGAI Yoshitaka 国立研究開発法人国立精神・神経医療研究センター, 神経研究所疾病研究第四部, 客員研究員 (60335354)
• Co-Investigator(Renkei-kenkyūsha): SEKI Kazuhiko 国立研究開発法人国立精神・神経医療研究センター, 神経研究所モデル動物研究部, 部長 (00226630) ; TOMIOKA Ikuo 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教 (30528196)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 神経科学 / 脳神経疾患 / ポリグルタミン病 / 疾患モデル / 霊長類 / マーモセット / 遺伝子 / 神経変性疾患

Outline of Final Research Achievements

In this study, aiming to establish non-human primate models of neurodegenerative diseases, we performed pathological analyses of transgenic marmoset models of Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3, one of the polyglutamine diseases. We found that three of seven SCA3 transgenic marmosets, which expressed the mutant ataxin-3 transgene at higher levels, gradually developed progressive neurological symptoms such as motor impairment and muscle weakness. Neuropathological examinations revealed significant neurodegeneration accompanied with polyglutamine inclusions in their brains. We therefore conclude that our SCA3 transgenic marmosets faithfully recapitulate human SCA3 patients’ features, and are useful models for elucidating the pathophysiological mechanisms of and developing clinically-applicable therapies for neurodegenerative diseases.

Free Research Field

神経内科学、神経科学、分子生物学