Structural and functional gastrointestinal abnormalities in ACTA2 R179H mice modeling multisystemic smooth muscle dysfunction syndrome

Seventy-five percent of patients with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) require medication for chronic constipation.

• ACTA2 mutations, including the R179H variant, alter smooth muscle contractility and actin filament stability.
• Patients with MSMDS show severe gut dysmotility, impacting their quality of life.
• ACTA2 mutant mice exhibit cecal and colonic dilatation, reduced intestinal length, and disrupted colonic migrating motor complexes.
• Delayed whole-gut transit and impaired contractile responses to stimulation were observed in the mouse model.
• Transcriptomic analysis revealed significant changes in genes related to the actin cytoskeleton in smooth muscle cells.
• Increased lymphocytic infiltration was identified through immune profiling, but no obvious changes were found in the enteric nervous system.

AI simplified