Novel Shank3 mutant exhibits behaviors with face validity for autism and altered striatal and hippocampal function

Thomas C. Jaramillo, Haley E. Speed, Zhong Xuan, Jeremy M. Reimers, Christine Ochoa Escamilla, Travis P. Weaver, Shunan Liu, Irina Filonova, Craig M. Powell

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Mutations/deletions in the SHANK3 gene are associated with autism spectrum disorders and intellectual disability. Here, we present electrophysiological and behavioral consequences in novel heterozygous and homozygous mice with a transcriptional stop cassette inserted upstream of the PDZ domain-coding exons in Shank3 (Shank3E13). Insertion of a transcriptional stop cassette prior to exon 13 leads to loss of the two higher molecular weight isoforms of Shank3. Behaviorally, both Shank3E13 heterozygous (HET) and homozygous knockout (KO) mice display increased repetitive grooming, deficits in social interaction tasks, and decreased rearing. Shank3E13 KO mice also display deficits in spatial memory in the Morris water maze task. Baseline hippocampal synaptic transmission and short-term plasticity are preserved in Shank3E13 HET and KO mice, while both HET and KO mice exhibit impaired hippocampal long-term plasticity. Additionally, Shank3E13 HET and KO mice display impaired striatal glutamatergic synaptic transmission. These results demonstrate for the first time in this novel Shank3 mutant that both homozygous and heterozygous mutation of Shank3 lead to behavioral abnormalities with face validity for autism along with widespread synaptic dysfunction. Autism Res 2017, 10: 42–65.

Original languageEnglish (US)
Pages (from-to)42-65
Number of pages24
JournalAutism Research
Issue number1
StatePublished - Jan 1 2017


  • Phelan-McDermid syndrome
  • Shank3
  • autism spectrum disorder
  • grooming
  • mouse model
  • social interaction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)


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