| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-02-15 |
| タイトル |
|
|
タイトル |
Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms |
| 言語 |
|
|
言語 |
eng |
| DOI |
|
|
|
関連識別子 |
https://doi.org/10.1523/ENEURO.0250-16.2017 |
|
|
関連名称 |
10.1523/ENEURO.0250-16.2017 |
| キーワード |
|
|
主題 |
Neurodegenerative disease, Polyglutamine disease, Transgenic monkey, Common marmoset |
| 資源タイプ |
|
|
資源 |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 著者 |
Tomioka, Ikuo
Ishibashi, Hidetoshi
Minakawa, Eiko N.
Motohashi, Hideyuki H.
Takayama, Osamu
Saito, Yuko
Popiel, H. Akiko
Puentes, Sandra
Owari, Kensuke
Nakatani, Terumi
Nogami, Naotake
Yamamoto, Kazuhiro
Noguchi, Satoru
Yonekawa, Takahiro
Tanaka, Yoko
Fujita, Naoko
Suzuki, Hikaru
Kikuchi, Hisae
Aizawa, Shu
Nagano, Seiichi
Yamada, Daisuke
Nishino, Ichizo
Ichinohe, Noritaka
Wada, Keiji
Kohsaka, Shinichi
Nagai, Yoshitaka
Seki, Kazuhiko
|
| 信州大学研究者総覧へのリンク |
|
|
氏名 |
Tomioka, Ikuo |
|
URL |
http://soar-rd.shinshu-u.ac.jp/profile/ja.WNAhPUkh.html |
| 出版者 |
|
|
出版者 |
Society for Neuroscience |
| 引用 |
|
|
内容記述 |
eNeuro.4(2):e0250(2017) |
| 書誌情報 |
eNeuro
巻 4,
号 2,
p. e0250,
発行日 2017-03-28
|
| 抄録 |
|
|
内容記述 |
Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases. |
| 資源タイプ（コンテンツの種類） |
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
2373-2822 |
| PubMed |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
https://pubmed.ncbi.nlm.nih.gov/28374014/ |
|
|
関連名称 |
28374014 |
| 権利 |
|
|
権利情報 |
Copyright © 2017 Tomioka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| WoS |
|
|
URL |
http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000397567900013 |
26870884_01.pdf (3.6 MB)
