Longitudinal analysis of motor symptoms and histopathology in woozy mice, a model of cerebellar ataxia

Neuroreport. 2017 Sep 6;28(13):779-787. doi: 10.1097/WNR.0000000000000816.

Abstract

Woozy (wz) mice develop ataxia and carry a mutation in the Sil1 gene. Homozygous wz mice have been characterized histopathologically, but no details of their motor function have been reported. In the present study, to comprehensively understand the relationship between symptomatic progression and pathological feature, we evaluated motor function and neurodegeneration with age from presymptomatic to terminal stages. We evaluated the motor function of homozygous and heterozygous wz mice aged from 5 to 71 weeks. Motor function was evaluated using the rotarod test, the footprint test, and the parallel rod floor test. Furthermore, we carried out a histopathological analysis of the mice at several ages. Impairment of motor function in homozygous wz mice began at around 11 weeks of age and became markedly worse until around 14 weeks. Heterozygous wz mice did not show motor dysfunction until 71 weeks of age. Features of cerebellar ataxia were evaluated using the footprint test and the parallel rod floor test. In addition to the observation of ubiquitin-positive aggregates at 6 weeks of age, Purkinje cell loss at 9 weeks of age and cerebellar atrophy were confirmed by histopathology. Apart from the cerebellar changes, we detected no other pathology that could contribute toward ataxia. In heterozygous wz mice, only minimal formation of ubiquitin-positive aggregates was observed. Homozygous wz mice showed adult-onset ataxia with progressive neurodegeneration of the cerebellum. Homozygous wz mice might be useful as an animal model of diseases showing adult-onset ataxia because of cerebellar neurodegeneration.

MeSH terms

  • Age Factors
  • Animals
  • Body Weight / genetics
  • Cerebellar Ataxia / complications*
  • Cerebellar Ataxia / genetics
  • Cerebellar Ataxia / pathology*
  • Cerebellum / metabolism
  • Cerebellum / pathology*
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gait / genetics
  • Gait / physiology*
  • Guanine Nucleotide Exchange Factors / genetics
  • Longitudinal Studies
  • Male
  • Mice
  • Mice, Mutant Strains
  • Movement Disorders / etiology*
  • Mutation / genetics
  • Rotarod Performance Test
  • Ubiquitin / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • SIL1 protein, mouse
  • Ubiquitin