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Am J Pathol. 2016 Sep;186(9):2254-61. doi: 10.1016/j.ajpath.2016.04.016. Epub 2016 Jul 16.

A Novel Mutation in Nucleoporin 35 Causes Murine Degenerative Colonic Smooth Muscle Myopathy.

Author information

1
Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia. Electronic address: ian.parish@anu.edu.au.
2
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
3
Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
4
Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
5
Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia; Garvan Institute of Medical Research, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
6
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia. Electronic address: h.young@unimelb.edu.au.

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.

Comment in

PMID:
27427419
PMCID:
PMC5012464
DOI:
10.1016/j.ajpath.2016.04.016
[Indexed for MEDLINE]
Free PMC Article

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