アマノ　ケンジ   Amano   天野　賢治    所属   東邦大学  医学部 医学科（大森病院）    職種   胚培養士
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Brain ventriculomegaly in Down syndrome mice is caused by Pcp4 dose-dependent cilia dysfunction.
掲載誌名	正式名：Human molecular genetics
掲載区分	国外
巻・号・頁	26(5),pp.923-931
著者・共著者	Matthieu Raveau,Takashi Nakahari,Sachie Asada,Keiichi Ishihara,Kenji Amano,Atsushi Shimohata,Haruhiko Sago,Kazuhiro Yamakawa
発行年月	2017/03/01
概要	Down syndrome is a leading cause of congenital intellectual disability caused by an additional copy of the chromosome 21. Patients display physiological and morphological changes affecting the brain and its function. Previously we showed that Ts1Cje and Ts2Cje, Down syndrome mouse models carrying overlapping trisomic segments of different length, show similar ventriculomegaly and neurogenesis dysfunction leading to the hypothesis of a cause-consequence relationship between these phenotypes. However, we here discovered that Ts1Rhr Down syndrome model, carrying an even shorter trisomic segment, was sufficient to trigger ventricular enlargement and ependymal cilia beating deficiency without affecting neurogenesis. We further found that Pcp4 gene on the Ts1Rhr trisomic segment is expressed in ependymal cells, and its resumption to two copies rescued both ventricular enlargement and cilia dysfunction in Ts1Rhr mice. This work underlines a Pcp4-dependent ciliopathy in Down syndrome brain affecting cerebrospinal fluid flow.
DOI	10.1093/hmg/ddx007
PMID	28069794