Details

Autor(en) / Beteiligte

• Wang, Shuo
• Tan, Ningdong
• Zhu, Xingliang
• Yao, Minghui
• Wang, Yaqing
• Zhang, Xiaohui
• Xu, Zhiheng

Titel

Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice

Ist Teil von

• Cell reports (Cambridge), 2018-12, Vol.25 (11), p.2963-2971.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 of Sh3rf2, which was detected in ASD patients, to determine whether Sh3rf2 is involved in brain development and whether mutation of SH3RF2 is causative for ASD and the mechanisms linking it to ASD traits. We find that mice with Sh3rf2 haploinsufficiency display significant deficits in social interaction and communication, as well as stereotyped or repetitive behaviors and hyperactivity and seizures. Disturbances in hippocampal dendritic spine development, aberrant composition of glutamatergic receptor subunits, and abnormal excitatory synaptic transmission were detected in heterozygous mutants. Remarkably, these defects are selectively unilateral. Our results support a notion that Sh3rf2 haploinsufficiency 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. [Display omitted] •Sh3rf2 is necessary for dendritic spine development and synaptogenesis•Sh3rf2 haploinsufficiency leads to autistic-like behaviors in mice•Disturbances in the hippocampal function of the heterozygote were selectively unilateral Wang et al. find that Sh3rf2 is important for neuron development and that Sh3rf2 haploinsufficiency in mice results in typical ASD-like behaviors, as well as selective unilateral disturbances in hippocampal dendritic spine development, composition of glutamatergic receptor subunits, and excitatory synaptic transmission.