Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model
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...
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MDPI AG
2019-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/9/2134 |
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| author | Ann Katrin Sauer Juergen Bockmann Konrad Steinestel Tobias M. Boeckers Andreas M. Grabrucker |
| author_facet | Ann Katrin Sauer Juergen Bockmann Konrad Steinestel Tobias M. Boeckers Andreas M. Grabrucker |
| author_sort | Ann Katrin Sauer |
| collection | DOAJ |
| description | 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 (<i>SHANK</i>) gene-family were identified in patients with ASD, and <i>Shank</i> 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 <i>Shank3</i> knock-out (KO) mice. Further, we detected a significantly altered microbiota composition measured in feces of <i>Shank3</i> KO mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher <i>E. coli</i> lipopolysaccharide levels in liver samples of <i>Shank3</i> KO mice, and detected an increase in Interleukin-6 and activated astrocytes in <i>Shank3</i> 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. |
| first_indexed | 2024-04-13T03:19:29Z |
| format | Article |
| id | doaj.art-50ef25c828324926902d8357d7ee0c13 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T03:19:29Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-50ef25c828324926902d8357d7ee0c132022-12-22T03:04:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01209213410.3390/ijms20092134ijms20092134Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse ModelAnn Katrin Sauer0Juergen Bockmann1Konrad Steinestel2Tobias M. Boeckers3Andreas M. Grabrucker4Cellular Neurobiology and Neuro-Nanotechnology lab, Dept. of Biological Sciences, University of Limerick, V94PH61 Limerick, IrelandInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyGerhard-Domagk-Institute of Pathology, Muenster University Medical Center, 48149 Münster, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyCellular Neurobiology and Neuro-Nanotechnology lab, Dept. of Biological Sciences, University of Limerick, V94PH61 Limerick, IrelandAutism 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 (<i>SHANK</i>) gene-family were identified in patients with ASD, and <i>Shank</i> 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 <i>Shank3</i> knock-out (KO) mice. Further, we detected a significantly altered microbiota composition measured in feces of <i>Shank3</i> KO mice that may contribute to inflammatory responses affecting brain development. In line with this, we found higher <i>E. coli</i> lipopolysaccharide levels in liver samples of <i>Shank3</i> KO mice, and detected an increase in Interleukin-6 and activated astrocytes in <i>Shank3</i> 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.https://www.mdpi.com/1422-0067/20/9/2134microbiomegutProSAP2Phelan McDermid Syndromegut–brain interactionleaky gutIL-6SHANK |
| spellingShingle | Ann Katrin Sauer Juergen Bockmann Konrad Steinestel Tobias M. Boeckers Andreas M. Grabrucker Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model International Journal of Molecular Sciences microbiome gut ProSAP2 Phelan McDermid Syndrome gut–brain interaction leaky gut IL-6 SHANK |
| title | Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model |
| title_full | Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model |
| title_fullStr | Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model |
| title_full_unstemmed | Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model |
| title_short | Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model |
| title_sort | altered intestinal morphology and microbiota composition in the autism spectrum disorders associated shank3 mouse model |
| topic | microbiome gut ProSAP2 Phelan McDermid Syndrome gut–brain interaction leaky gut IL-6 SHANK |
| url | https://www.mdpi.com/1422-0067/20/9/2134 |
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