SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice

Summary: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neur...

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Autores principales:	Kan Yang, Yuhan Shi, Xiujuan Du, Jincheng Wang, Yuefang Zhang, Shifang Shan, Yiting Yuan, Ruoqing Wang, Chenhuan Zhou, Yuting Liu, Zilin Cai, Yanzhi Wang, Liu Fan, Huatai Xu, Juehua Yu, Jinke Cheng, Fei Li, Zilong Qiu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6b7fd11d03ff423a94c2cbfb7a590876
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spelling	oai:doaj.org-article:6b7fd11d03ff423a94c2cbfb7a5908762021-11-04T04:29:28ZSENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice2211-124710.1016/j.celrep.2021.109939https://doaj.org/article/6b7fd11d03ff423a94c2cbfb7a5908762021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014121https://doaj.org/toc/2211-1247Summary: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1+/− mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1+/− mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1+/− mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.Kan YangYuhan ShiXiujuan DuJincheng WangYuefang ZhangShifang ShanYiting YuanRuoqing WangChenhuan ZhouYuting LiuZilin CaiYanzhi WangLiu FanHuatai XuJuehua YuJinke ChengFei LiZilong QiuElsevierarticleBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109939- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Kan Yang Yuhan Shi Xiujuan Du Jincheng Wang Yuefang Zhang Shifang Shan Yiting Yuan Ruoqing Wang Chenhuan Zhou Yuting Liu Zilin Cai Yanzhi Wang Liu Fan Huatai Xu Juehua Yu Jinke Cheng Fei Li Zilong Qiu SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
description	Summary: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1+/− mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1+/− mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1+/− mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.
format	article
author	Kan Yang Yuhan Shi Xiujuan Du Jincheng Wang Yuefang Zhang Shifang Shan Yiting Yuan Ruoqing Wang Chenhuan Zhou Yuting Liu Zilin Cai Yanzhi Wang Liu Fan Huatai Xu Juehua Yu Jinke Cheng Fei Li Zilong Qiu
author_facet	Kan Yang Yuhan Shi Xiujuan Du Jincheng Wang Yuefang Zhang Shifang Shan Yiting Yuan Ruoqing Wang Chenhuan Zhou Yuting Liu Zilin Cai Yanzhi Wang Liu Fan Huatai Xu Juehua Yu Jinke Cheng Fei Li Zilong Qiu
author_sort	Kan Yang
title	SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
title_short	SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
title_full	SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
title_fullStr	SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
title_full_unstemmed	SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
title_sort	senp1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6b7fd11d03ff423a94c2cbfb7a590876
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SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice

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