Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice (Cell Reports 2018, 25:2963–2971)

報告日期: 2019/04/19
報告時間: 17:10/18:00
報告學生: 劉嘉瑋
講評老師: 蕭雅心

Sh3rf2 haploinsufficiency leads to unilateral neuronal development deficits and autistic-like behaviors in mice

Wang et al., 2018, Cell Reports 25, 2963–2971

Speaker: Chia-Wei Liou; Commentator: Ya-Hsin Hsiao Ph.D.

Autism spectrum disorder (ASD) is a complex children-onset brain developmental disorder with delayed language, restricted ranged of interests, repetitive behaviors and deficit in social interaction. Previous study has identified new candidate ASD-risk genes by sequencing 5205 samples from families with ASD, including SH3RF2 [1]. A clinical case report indicated that the 1.8-Mb microdeletion of SH3RF2 at chromosome 5q32 was found in a patient with ASD and his father [2]. However, the neural mechanism by which deletionof SH3RF2 causes ASD-like behaviors is not well studied. Thus, this study aimed to investigate the role of SH3RF2 in ASD-like behaviors and hippocampal function. To answer the question, the author generated Sh3rf2 haploinsufficiency mice. First, they found that Sh3rf2+/- mice exhibited ASD-like behaviors, including impaired sociability, social novelty and ultrasonic vocalization communication and increased repetitive/stereotypic behaviors. Sh3rf2+/- mice displayed the reduction of dendritic spine volume in left hippocampus CA1 pyramidal neurons, but not in right side. In addition, NR2A and GluR2 protein levels were increased at the postsynaptic density in left and right hippocampus, respectively. Lastly, the authors evaluated the synaptic transmission by whole-cell recording in left and right hippocampal CA1 region. They found that Sh3rf2+/- displayed altered and asymmetric results in the left and right hippocampal CA1 region, including membrane properties and AMPA receptor-mediated excitatory synaptic inputs. This study demonstrated that mutation of Sh3rf2 in mice leaded to ASD-like behaviors, abnormal synaptogenesis and altered electrophysiological properties in hippocampus. The Sh3rf2+/- mice could be an ASD animal model to discover the etiology of ASD.   

  1. RK, C.Y., et al., Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci, 2017. 20(4): p. 602-611.
  2. Gau, S.S., et al., Identification of two inherited copy number variants in a male with autism supports two-hit and compound heterozygosity models of autism. Am J Med Genet B Neuropsychiatr Genet, 2012. 159b(6): p. 710-7.