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

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. (Am J Pathol 2016 http://dx

The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds

“…Two such candidate genes involved in muscle differentiation include BIN1 and NUP35 . Variants within BIN1 and NUP35 on OAR2 have been previously associated with muscle myopathy in humans and mice, although their role in sheep is unknown [ 66 , 67 ]. However, it most likely that the nucleoporin NUP35 plays an important role in myogenic differentiation through the formation of the nuclear pore complex [ 49 ].…”

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“…Their amplitude is consistently smaller of two order of magnitudes than endogenous pulsatile ones, because the 1kPa stress is here magnetically produced directly in the conjunctive epithelial tissue that includes epithelial crypts only. Indeed, the latter is ten times thinner than the visceral smooth muscle from which the 1kPa stress produces the endogenous peristatic movements imposed to the conjonctive and crypt tissues 35 (see Supplementary Note 3d ). Thus, the magnetic treatment does not rescue the physiological amplitude and propagative nature of the overall colonic structure pulsatile movements, but rescues in the conjonctive and epithelial cells of interest the physiological pulsatile 1 kPa high-frequency stress pressure of 2 s generated by associated physiological movements.…”