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Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3b mutant model of autism.


ABSTRACT: Background and aims:Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the SHANK3 gene. Methods:To generate a zebrafish model of PMS, we used CRISPR/Cas9 to introduce clinically related C-terminal frameshift mutations in shank3a and shank3b zebrafish paralogues (shank3ab?C). Because PMS is caused by SHANK3 haploinsufficiency, we assessed the digestive tract (DT) structure and function in zebrafish shank3ab?C +/- heterozygotes. Human SHANK3 mRNA was then used to rescue DT phenotypes in larval zebrafish. Results:Significantly slower rates of DT peristaltic contractions (p?

SUBMITTER: James DM 

PROVIDER: S-EPMC6357389 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Intestinal dysmotility in a zebrafish (<i>Danio rerio</i>) <i>shank3a;shank3b</i> mutant model of autism.

James David M DM   Kozol Robert A RA   Kajiwara Yuji Y   Wahl Adam L AL   Storrs Emily C EC   Buxbaum Joseph D JD   Klein Mason M   Moshiree Baharak B   Dallman Julia E JE  

Molecular autism 20190131


<h4>Background and aims</h4>Autism spectrum disorder (ASD) is currently estimated to affect more than 1% of the world population. For people with ASD, gastrointestinal (GI) distress is a commonly reported but a poorly understood co-occurring symptom. Here, we investigate the physiological basis for GI distress in ASD by studying gut function in a zebrafish model of Phelan-McDermid syndrome (PMS), a condition caused by mutations in the <i>SHANK3</i> gene.<h4>Methods</h4>To generate a zebrafish mo  ...[more]

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