title: 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.
authors.affiliation: 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.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Parish
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lincon A
authors.initials: LA
authors.lastname: Stamp
authors.affiliation: Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Ayla May D
authors.initials: AM
authors.lastname: Lorenzo
authors.affiliation: Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Fowler
authors.affiliation: Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Yovina
authors.initials: Y
authors.lastname: Sontani
authors.affiliation: Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miosge
authors.affiliation: Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Debbie R
authors.initials: DR
authors.lastname: Howard
authors.affiliation: 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.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia. Electronic address: h.young@unimelb.edu.au.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Young
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003112:Colonic Pseudo-Obstruction / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D017354:Point Mutation
chemical_list: D028861:Nuclear Pore Complex Proteins