title: A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration.
abstract: BACKGROUND
  A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and histological features with polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV), a recently described hereditary disease in Black Russian Terriers (BRTs). Dogs with POANV harbor mutations in RAB3GAP1 which codes for a protein involved in membrane trafficking.
  
  
  OBJECTIVE
  Rottweilers with NVSD will be homozygous for the RAB3GAP1:c.743delC allele associated with POANV in BRTs.
  
  
  METHODS
  Eight Rottweilers with NVSD confirmed at necropsy, 128 Rottweilers without early onset neurologic signs, and 468 randomly selected dogs from 169 other breeds.
  
  
  METHODS
  Retrospective case-control study. Dogs were genotyped for the RAB3GAP1:c.743delC allele with an allelic discrimination assay.
  
  
  RESULTS
  All 8 NVSD-affected dogs were homozygous for the RAB3GAP1:c.743delC allele while the 128 NVSD-free Rottweilers were either homozygous for the reference allele (n = 105) or heterozygous (n = 23) and the 468 genotyped dogs from other breeds were all homozygous for the reference allele.
  
  
  CONCLUSIONS
  The RAB3GAP1:c.743delC mutation is associated with a similar phenotype in Rottweilers and BRTs. Identification of the mutation permits a DNA test that can aid in the diagnosis of NVSD and identify carriers of the trait so that breeders can avoid producing affected dogs. Disruption of membrane trafficking could explain the neuronal vacuolation seen in NVSD and other spongiform encephalopathies.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: T
authors.initials: T
authors.lastname: Mhlanga-Mutangadura
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: G S
authors.initials: GS
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: A
authors.initials: A
authors.lastname: Ashwini
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA.
authors.forename: G D
authors.initials: GD
authors.lastname: Shelton
authors.affiliation: Department of Clinical Sciences, Colorado State University, Fort Collins, CO.
authors.forename: S A
authors.initials: SA
authors.lastname: Wennogle
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: G C
authors.initials: GC
authors.lastname: Johnson
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: K
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: D P
authors.initials: DP
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D005838:Genotype; D009154:Mutation; D009474:Neurons / Q000473:pathology; D011115:Polyneuropathies / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D012189:Retrospective Studies; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D020692:rab3 GTP-Binding Proteins / Q000235:genetics*
chemical_list: D020692:rab3 GTP-Binding Proteins
keywords: Canine; Molecular genetics; Peripheral nervous system disorders; Rab GTPase; Spongiform encephalopathies; Warburg micro syndrome