A novel mutation in the nucleoporin NUP35 causes murine degenerative colonic smooth muscle myopathy

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare, but life-threatening, disease characterized by severe intestinal dysmotility. Histopathological studies of CIPO patients have identified several different mechanisms that appear to be responsible for 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 reduced lifespan. Histopathological 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 sub-type of CIPO characterized by degenerative myopathy. Our study also raises the possibility that Nup35 polymorphisms could contribute to some cases of CIPO. 2 not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/036582 doi: bioRxiv preprint first posted online Jan. 13, 2016;