Shank3 mutation manifests in abnormal gastrointestinal morphology and function in mice

Area of Science:

• Neuroscience
• Gastroenterology
• Genetics

Background:

• Gastrointestinal (GI) comorbidities are frequently observed in individuals with Autism Spectrum Disorder (ASD).
• The underlying causes of these GI issues in ASD remain largely unknown.
• Shank3B mutant mice serve as a key genetic model for studying ASD.

Purpose of the Study:

• To investigate potential alterations in GI morphology and function in Shank3B mutant mice.
• To identify mechanisms linking Shank3 gene mutations to GI comorbidities in ASD.

Main Methods:

• Histological analysis (H&E staining, immunohistochemistry) of GI and enteric nervous system morphology.
• Assessment of GI permeability using FITC-Dextran assay.
• Evaluation of whole-GI tract motility in vivo and colonic contractions ex vivo.

Main Results:

• Shank3B knockout mice displayed significant changes in epithelial morphology and increased GI permeability.
• Increased myenteric plexus density and neuronal markers (HuC/D) were noted in the colon.
• These mice exhibited delayed GI transit and impaired colonic contractions, with heterozygous mice showing milder effects.

Conclusions:

• Shank3B mutations lead to significant alterations in GI morphology and function.
• The Shank3 gene is crucial for normal GI tract function.
• Mutations in Shank3 may play a role in the development of GI comorbidities associated with ASD.