Altered intestinal morphology and microbiota composition in the autism spectrum disorders associated SHANK3 mouse model

Ann Katrin Sauer, Juergen Bockmann, Konrad Steinestel, Tobias M. Boeckers, Andreas M. Grabrucker

Research output: Contribution to journalArticlepeer-review

Abstract

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by deficits in social interaction and communication, and repetitive behaviors. In addition, co-morbidities such as gastro-intestinal problems have frequently been reported. Mutations and deletion of proteins of the SH3 and multiple ankyrin repeat domains (SHANK) gene-family were identified in patients with ASD, and Shank knock-out mouse models display autism-like phenotypes. SHANK3 proteins are not only expressed in the central nervous system (CNS). Here, we show expression in gastrointestinal (GI) epithelium and report a significantly different GI morphology in Shank3 knock-out (KO) mice. Further, we detected a significantly altered microbiota composition measured in feces of Shank3 KO mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher E. coli lipopolysaccharide levels in liver samples of Shank3 KO mice, and detected an increase in Interleukin-6 and activated astrocytes in Shank3 KO mice. We conclude that apart from its well-known role in the CNS, SHANK3 plays a specific role in the GI tract that may contribute to the ASD phenotype by extracerebral mechanisms.

Original languageEnglish
Article number2134
JournalInternational Journal of Molecular Sciences
Volume20
Issue number9
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • Gut
  • Gut-brain interaction
  • IL-6
  • Leaky gut
  • Microbiome
  • Phelan mcdermid syndrome
  • ProSAP2
  • SHANK

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