title: Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
abstract: Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: João
authors.initials: J
authors.lastname: Peça
authors.forename: Cátia
authors.initials: C
authors.lastname: Feliciano
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Ting
authors.forename: Wenting
authors.initials: W
authors.lastname: Wang
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wells
authors.forename: Talaignair N
authors.initials: TN
authors.lastname: Venkatraman
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lascola
authors.forename: Zhanyan
authors.initials: Z
authors.lastname: Fu
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003192:Compulsive Behavior / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006120:Grooming; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D017072:Neostriatum / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins; D009434:Neural Pathways; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016728:Self-Injurious Behavior / Q000235:genetics / Q000503:physiopathology; D012919:Social Behavior; D013569:Synapses / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C492356:Shank3 protein, mouse