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Updated: Mar 17, 2026
Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice
Published on: February 3, 2016
A Novel Mutation in Nucleoporin 35 Causes Murine Degenerative Colonic Smooth Muscle Myopathy
Ian A Parish1, Lincon A Stamp2, Ayla May D Lorenzo3
1Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Abstract:
Chronic intestinal pseudo-obstruction (CIPO) is a rare but life-threatening disease characterized by severe intestinal dysmotility. Histopathologic studies in CIPO patients have identified several different mechanisms that appear to be involved in the dysmotility, including defects in neurons, smooth muscle, or interstitial cells of Cajal. Currently there are few mouse models of the various forms of CIPO. We generated a mouse with a point mutation in the RNA recognition motif of the Nup35 gene, which encodes a component of the nuclear pore complex. Nup35 mutants developed a severe megacolon and exhibited a reduced lifespan. Histopathologic examination revealed a degenerative myopathy that developed after birth and specifically affected smooth muscle in the colon; smooth muscle in the small bowel and the bladder were not affected. Furthermore, no defects were found in enteric neurons or interstitial cells of Cajal. Nup35 mice are likely to be a valuable model for the subtype of CIPO characterized by degenerative myopathy. Our study also raises the possibility that Nup35 polymorphisms could contribute to some cases of CIPO.
Insights
A new Nup35 mouse model develops severe megacolon and a degenerative myopathy, offering insights into chronic intestinal pseudo-obstruction (CIPO) subtypes. This model may help understand CIPO caused by smooth muscle defects.
Area of Science:
- Genetics and Molecular Biology
- Gastroenterology
- Pathology
Background:
- Chronic intestinal pseudo-obstruction (CIPO) is a rare, severe gastrointestinal motility disorder.
- CIPO pathogenesis involves neuronal, smooth muscle, or interstitial cells of Cajal defects.
- Existing mouse models for CIPO subtypes are limited.
Purpose of the Study:
- To create and characterize a novel mouse model for CIPO.
- To investigate the role of Nup35 gene mutations in intestinal dysmotility.
- To explore potential genetic contributions to CIPO.
Main Methods:
- Generated a mouse model with a point mutation in the Nup35 gene's RNA recognition motif.
- Assessed Nup35 mutant mice for megacolon, lifespan, and histopathologic changes.
- Examined enteric neurons and interstitial cells of Cajal in affected mice.
Main Results:
- Nup35 mutant mice exhibited severe megacolon and reduced lifespan.
- Histopathology revealed a postnatal degenerative myopathy specifically affecting colonic smooth muscle.
- No defects were observed in enteric neurons or interstitial cells of Cajal.
Conclusions:
- Nup35 mutant mice represent a valuable model for CIPO associated with degenerative myopathy.
- The study highlights the potential role of Nup35 gene defects in CIPO pathogenesis.
- Nup35 polymorphisms may contribute to certain CIPO cases.
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