Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice

Abstract 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 effe...

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Autores principales:	Shuichi Hayashi, Yoko Inoue, Satoko Hattori, Mari Kaneko, Go Shioi, Tsuyoshi Miyakawa, Masatoshi Takeichi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c80289a658c41e5abfec08cd1b0f138
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spelling	oai:doaj.org-article:2c80289a658c41e5abfec08cd1b0f1382021-12-02T15:05:43ZLoss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice10.1038/s41598-017-06374-x2045-2322https://doaj.org/article/2c80289a658c41e5abfec08cd1b0f1382017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06374-xhttps://doaj.org/toc/2045-2322Abstract 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.Shuichi HayashiYoko InoueSatoko HattoriMari KanekoGo ShioiTsuyoshi MiyakawaMasatoshi TakeichiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuichi Hayashi Yoko Inoue Satoko Hattori Mari Kaneko Go Shioi Tsuyoshi Miyakawa Masatoshi Takeichi Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
description	Abstract 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.
format	article
author	Shuichi Hayashi Yoko Inoue Satoko Hattori Mari Kaneko Go Shioi Tsuyoshi Miyakawa Masatoshi Takeichi
author_facet	Shuichi Hayashi Yoko Inoue Satoko Hattori Mari Kaneko Go Shioi Tsuyoshi Miyakawa Masatoshi Takeichi
author_sort	Shuichi Hayashi
title	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
title_short	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
title_full	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
title_fullStr	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
title_full_unstemmed	Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
title_sort	loss of x-linked protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2c80289a658c41e5abfec08cd1b0f138
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Loss of X-linked Protocadherin-19 differentially affects the behavior of heterozygous female and hemizygous male mice

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