Cell Reports
Abstract
Autism spectrum disorders (ASDs) include a variety of developmental brain disorders with clinical findings implicating the dysfunction of the left hemisphere. Here, we generate mice lacking one copy ofSh3rf2, which was detected in ASD patients, to determine whether Sh3rf2 is involved in brain development and whether mutation ofSH3RF2is causative for ASD and the mechanisms linking it to ASD traits. We find that mice withSh3rf2haploinsufficiency display significant deficits in social interactionand communication, as well as stereotyped orrepetitive behaviors and hyperactivity and seizures. Disturbances in hippocampal dendritic spine development, aberrant composition of glutamatergic receptor subunits, and abnormal excitatory synaptictransmission were detected in heterozygous mutants. Remarkably, these defects are selectively unilateral. Our results support a notion thatSh3rf2haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis most likely resulting from deficits in synaptic function in the left hemisphere of the brain.
| 论文编号: | DOI:10.1016/j.celrep.2018.11.044 |
| 论文题目: | Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice |
| 英文论文题目: | Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice |
| 第一作者: | Shuo Wang, Ningdong Tan, Xingliang Zhu, Minghui Yao, Yaqing Wang, Xiaohui Zhang, Zhiheng Xu |
| 英文第一作者: | Shuo Wang, Ningdong Tan, Xingliang Zhu, Minghui Yao, Yaqing Wang, Xiaohui Zhang, Zhiheng Xu |
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| 发表年度: | 2018-12-12 |
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| 摘要: | Autism spectrum disorders (ASDs) include a variety of developmental brain disorders with clinical findings implicating the dysfunction of the left hemisphere. Here, we generate mice lacking one copy ofSh3rf2, which was detected in ASD patients, to determine whether Sh3rf2 is involved in brain development and whether mutation ofSH3RF2is causative for ASD and the mechanisms linking it to ASD traits. We find that mice withSh3rf2haploinsufficiency display significant deficits in social interactionand communication, as well as stereotyped orrepetitive behaviors and hyperactivity and seizures. Disturbances in hippocampal dendritic spine development, aberrant composition of glutamatergic receptor subunits, and abnormal excitatory synaptictransmission were detected in heterozygous mutants. Remarkably, these defects are selectively unilateral. Our results support a notion thatSh3rf2haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis most likely resulting from deficits in synaptic function in the left hemisphere of the brain. |
| 英文摘要: | Autism spectrum disorders (ASDs) include a variety of developmental brain disorders with clinical findings implicating the dysfunction of the left hemisphere. Here, we generate mice lacking one copy ofSh3rf2, which was detected in ASD patients, to determine whether Sh3rf2 is involved in brain development and whether mutation ofSH3RF2is causative for ASD and the mechanisms linking it to ASD traits. We find that mice withSh3rf2haploinsufficiency display significant deficits in social interactionand communication, as well as stereotyped orrepetitive behaviors and hyperactivity and seizures. Disturbances in hippocampal dendritic spine development, aberrant composition of glutamatergic receptor subunits, and abnormal excitatory synaptictransmission were detected in heterozygous mutants. Remarkably, these defects are selectively unilateral. Our results support a notion thatSh3rf2haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis most likely resulting from deficits in synaptic function in the left hemisphere of the brain. |
| 刊物名称: | Cell Reports |
| 英文刊物名称: | Cell Reports |
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| 其它备注: | Shuo Wang, Ningdong Tan, Xingliang Zhu, Minghui Yao, Yaqing Wang, Xiaohui Zhang, Zhiheng Xu. Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice. Cell Reports. DOI:10.1016/j.celrep.2018.11.044. |
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