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Open AccessArticle

Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model

1
Cellular Neurobiology and Neuro-Nanotechnology lab, Dept. of Biological Sciences, University of Limerick, V94PH61 Limerick, Ireland
2
Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany
3
Gerhard-Domagk-Institute of Pathology, Muenster University Medical Center, 48149 Münster, Germany
4
Health Research Institute (HRI), University of Limerick, V94PH61 Limerick, Ireland
5
Bernal Institute, University of Limerick, V94PH61 Limerick, Ireland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2134; https://doi.org/10.3390/ijms20092134
Received: 27 February 2019 / Revised: 26 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
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. View Full-Text
Keywords: microbiome; gut; ProSAP2; Phelan McDermid Syndrome; gut–brain interaction; leaky gut; IL-6; SHANK microbiome; gut; ProSAP2; Phelan McDermid Syndrome; gut–brain interaction; leaky gut; IL-6; SHANK
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Sauer, A.K.; Bockmann, J.; Steinestel, K.; Boeckers, T.M.; Grabrucker, A.M. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int. J. Mol. Sci. 2019, 20, 2134.

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