ハヤシ　シュウイチ   Shuichi Hayashi   林　周一    所属   川崎医科大学  医学部 基礎医学　解剖学    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice.
掲載誌名	正式名：Scientific Reports
掲載区分	国外
巻・号・頁	7(1),pp.5801
著者・共著者	Hayashi, S., Inoue, Y., Hattori, S., Kaneko, M., Shioi, G., Miyakawa, T., Takeichi, M.
担当区分	筆頭著者,責任著者
発行年月	2017
概要	Mutations in the X-linked gene Protocadherin-19 (Pcdh19) cause female-limited epilepsy and mental retardation in humans. Although Pcdh19 is known to be a homophilic cell-cell adhesion molecule, how its mutations bring about female-specific disorders remains elusive. Here, we report the effects of Pcdh19 knockout in mice on their development and behavior. Pcdh19 was expressed in various brain regions including the cerebral cortex and hippocampus. Although Pcdh19-positive cells were evenly distributed in layer V of wild-type cortices, their distribution became a mosaic in Pcdh19 heterozygous female cortices. In cortical and hippocampal neurons, Pcdh19 was localized along their dendrites, showing occasional accumulation on synapses. Pcdh19 mutants, however, displayed no detectable abnormalities in dendrite and spine morphology of layer V neurons. Nevertheless, Pcdh19 hemizygous males and heterozygous females showed impaired behaviors including activity defects under stress conditions. Notably, only heterozygous females exhibited decreased fear responses. In addition, Pcdh19 overexpression in wild-type cortices led to ectopic clustering of Pcdh19-positive neurons. These results suggest that Pcdh19 is required for behavioral control in mice, but its genetic loss differentially affects the male and female behavior, as seen in human, and they also support the hypothesis that the mosaic expression of Pcdh19 in brains perturbs neuronal interactions.