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 di erent 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 a ecting 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
History
Publication
International Journal of Molecular Sciences;20,pp. 2134-2149