Can colonic migrating motor complexes occur in mice lacking the endothelin-3 gene?

Area of Science:

• Gastroenterology
• Developmental biology
• Neuroscience

Background:

• Colonic migrating motor complexes (CMMC) are crucial for fecal expulsion in mammals.
• Endothelin-3 mutations cause severe colonic aganglionosis and lethality in mice.
• Lethal-spotted (ls/ls) mice, a C57BL6 background strain with endothelin-3 deficiency, exhibit prolonged survival, but CMMC function remains uncharacterized.

Purpose of the Study:

• To investigate the existence and characteristics of CMMC in the colons of ls/ls mice.
• To determine if CMMC generation is preserved in ls/ls mice.
• To assess the relationship between aganglionosis length and CMMC presence/frequency.

Main Methods:

• Spatiotemporal mapping of colonic wall movements in isolated wild-type and ls/ls mouse colons.
• Mechanical recordings of colonic motility.
• Analysis of CMMC existence, frequency, and propagation velocity.

Main Results:

• ls/ls mice, despite having megacolon, generate CMMC within their ganglionic colonic segments.
• CMMC occasionally propagated into the aganglionic regions.
• Aganglionosis length showed a weak correlation with CMMC existence or frequency.
• CMMC propagation velocity was reduced in ls/ls mice when stimulated by intraluminal fluid.
• A myogenic motor pattern was observed in the aganglionic colon.

Conclusions:

• ls/ls mice retain CMMC generation in the ganglionic colon, which is sufficient for survival.
• Propulsive motility in the ganglionic segment allows ls/ls mice to achieve a normal lifespan.
• Fatal bowel obstruction is rare in these mice due to preserved CMMC function.