科学研究

报告预告

SHANK3突变猕猴的类自闭症行为和其非典型脑连接

    |    分享:
2019-10-24


Seminar Type

B-type

Preferred Location

Third Floor Lecture Hall, Jianzan Building (Phase I)

Chinese Institute for Brain Research, Beijing

Time

11:00-12:00  Monday,October 28th, 2019

Speaker

Yang Zhou, Ph.D.

Assistant Professor

Montreal Neurological Institute

McGill University

 


周扬,博士

麦吉尔大学

蒙特利尔神经病学研究所

助理教授


Host

Dr. Ying Li

Topic

Autistic-like Behaviors and Atypical Brain Connectivity in SHANK3 Mutant macaques


SHANK3突变猕猴的类自闭症行为和其非典型脑连接

Abstract

Mutation or disruption of the SHANK3 (SH3 domain and ankyrin repeat) gene at the 22q13.3 locus represents a highly penetrant, monogenic risk-factor for Autism Spectrum Disorder (ASD) and is a leading cause of Phelan–McDermid Syndrome (PMS). Recent advances in gene editing enabled the creation of genetically engineered non-human primate (NHP) models of brain disorders. Such NHP models might better approximate some neural and behavioral features of ASD than rodents and allow for gaining a better neurobiological understanding of ASD as well as developing treatment strategies. I will be presenting a collaborative effort led by Guoping Feng and Robert Desimon on a study of macaque monkeys carrying germline-transmissible SHANK3 mutation generated with CRISPR/Cas9-mediated gene editing. The founder mutants exhibited sleep disturbances, motor deficits, and increased repetitive behaviors, as well as social and learning impairments. Examining resting-state brain activity in founder monkeys with functional magnetic resonance imaging revealed altered local and global connectivity patterns indicative of circuit abnormalities. Our findings of altered brain connectivity and compromised behavioral performance in SHANK3 mutant macaques parallel some aspects of the gene-circuit-behavior dysfunction in human ASD and PMS.  


SHANK3(SH3结构域和锚蛋白重复序列)基因的22q13.3位点发生突变或破坏预示着自闭症谱系障碍(ASD)的高渗透性,并具有单基因突变患病风险,这是导致Phelan–McDermid综合征(PMS)的主要原因。基因编辑的最新进展能够做到创建遗传工程化的非人灵长类(NHP)脑疾病模型。这样的NHP模型可以比啮齿动物更好地近似ASD的某些神经和行为特征,并且可以更好地了解ASD的神经生物学知识并制定治疗计划。我将展示由Guoping Feng和Robert Desimon领导的一项合作研究,该研究以含有CRISPR / Cas9基因编辑的可在种系内传递的SHANK3突变的猕猴作为研究对象。首建突变体表现出睡眠障碍,运动障碍,重复行为增加以及社交和学习障碍。用功能磁共振成像检查首建猴的静息态大脑活动,发现局部和全局连接模式发生了变化,这提示环路异常我们在SHANK3突变猕猴中发现的大脑连接模式的改变和代偿性行为与人类ASD和PMS中基因-环路-行为功能障碍的某些方面相类似。

Speaker

Biography

A. PROFESSIONAL PREPARATION

 

College/University             Major          Degree/Year 

 

Bengbu Medical College, China   Medicine        BA/2002  

 

Institute of Neuroscience, CAS   Neurobiology     Ph.D./2008       Shanghai, China    

 

B. ACADEMIC/PROFESSIONAL APPOINTMENTS

 

Assistant Professor,                         04/2019-Present

Montreal Neurological Institute,

McGill University                                    

 

Research Scientist,                          04/2014-03/2019

McGovern Institute at MIT                                                          

 

Postdoctoral Fellow                         01/2011-04/2014

(Drs. Feng Zhang and Guoping Feng lab at MIT)                      

 

Assistant Investigator/Viral Core Facility         03/2008-12/2010                                                                  Institute of Neuroscience, CAS, Shanghai, China