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Nature DOI:10.1038/nature09965

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.

Publication TypeJournal Article
Year of Publication2011
AuthorsPeça, J, Feliciano, C, Ting, JT, Wang, W, Wells, MF, Venkatraman, TN, Lascola, CD, Fu, Z, Feng, G
Date Published2011 Apr 28
KeywordsAnimals, Autistic Disorder, Carrier Proteins, Compulsive Behavior, Female, Gene Deletion, Grooming, Male, Mice, Mutant Proteins, Neostriatum, Nerve Tissue Proteins, Neural Pathways, RNA, Messenger, Self-Injurious Behavior, Social Behavior, Synapses

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.


Alternate JournalNature
PubMed ID21423165
PubMed Central IDPMC3090611
Grant ListR01 MH081201-05 / MH / NIMH NIH HHS / United States
R03 MH085224 / MH / NIMH NIH HHS / United States
R01MH081201 / MH / NIMH NIH HHS / United States
R03MH085224 / MH / NIMH NIH HHS / United States
F32MH084460 / MH / NIMH NIH HHS / United States
R01 MH081201 / MH / NIMH NIH HHS / United States
F32 MH084460 / MH / NIMH NIH HHS / United States