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	DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile seizures.
掲載誌名	正式名：Neurobiology of disease
掲載区分	国外
巻・号・頁	110,pp.180-191
著者・共著者	Matthieu Raveau,Atsushi Shimohata,Kenji Amano,Hiroyuki Miyamoto,Kazuhiro Yamakawa
発行年月	2018/02
概要	Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a+/- mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts. Susceptibility to hyperthermia-induced seizures was also significantly increased in these mice. The truncation leading to haploinsufficiency of DYRK1A in mice thus recapitulates the syndromic phenotypes observed in human patients and constitutes a useful model for further investigations of the mechanisms leading to ASD, speech delay and febrile seizures.
DOI	10.1016/j.nbd.2017.12.003
PMID	29223763