title: Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease.
abstract: Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood.
  
  
  
  Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice.
  
  
  
  Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice.
  
  
  
  For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Armao
authors.affiliation: Gene Therapy Center, University of North Carolina at Chapel Hill, 7119 Thurston Bowles, Campus Box 7352, Chapel Hill, NC, 27599-7352, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Bailey
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bouldin
authors.affiliation: Research Institute for Veterinary Sciences and Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Yongbaek
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Gene Therapy Center, University of North Carolina at Chapel Hill, 7119 Thurston Bowles, Campus Box 7352, Chapel Hill, NC, 27599-7352, USA. graysj@email.unc.edu.|Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. graysj@email.unc.edu.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gray
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000473:pathology / Q000503:physiopathology*; D001835:Body Weight; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D017615:Enteric Nervous System / Q000473:pathology / Q000503:physiopathology; D005243:Feces / Q000737:chemistry; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology / Q000503:physiopathology; D056768:Giant Axonal Neuropathy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010275:Parasympathetic Nervous System / Q000473:pathology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000473:pathology / Q000503:physiopathology; D014551:Urinary Tract / Q000473:pathology / Q000503:physiopathology
keywords: Autonomic nervous system; Giant axonal neuropathy; Gigaxonin; Intermediate filaments; Neurodegenerative disease