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

Ian A. Parish*, Lincon A. Stamp, Ayla May D. Lorenzo, Suzanne M. Fowler, Yovina Sontani, Lisa A. Miosge, Debbie R. Howard, Christopher C. Goodnow, Heather M. Young, John B. Furness

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)2254-2261
    Number of pages8
    JournalAmerican Journal of Pathology
    Issue number9
    Publication statusPublished - 1 Sept 2016


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