X-linked transmission of the shaker mutation in rats with hereditary Purkinje cell degeneration and ataxia

Brain Res. 2000 Mar 10;858(2):264-73. doi: 10.1016/s0006-8993(99)02415-4.

Abstract

This study reports on the mode of inheritance of the shaker mutation and the development of an inbred strain of the shaker rat mutation from Sprague Dawley outbred stock onto a Wistar Furth background. Neuroanatomical and behavioral expression of the affected phenotype, through seven generations of backcross and intercross breeding, has confirmed the mode of inheritance to be X-linked. Behaviorally, affected mutants present with a wide-based ataxic gait and whole body tremor. In affected mutants calbindin immunostaining for surviving cerebellar Purkinje cells revealed widespread degeneration in the anterior lobe and in limited areas of the posterior lobe. Fast Fourier transform analysis of the tremor revealed a frequency of 3-5 Hz. As predicted by X-linked inheritance, female descendants of an affected male are carriers for the genotype and the phenotype is expressed in one-half of her male offspring. There was spatially random and limited degeneration of Purkinje cells in carrier females, but they did not display overt clinical signs of ataxia and tremor. These data provide further support for using the shaker mutant rat as an animal model for studies of mechanisms underlying human heredodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / pathology
  • Cerebellar Ataxia / physiopathology
  • Disease Models, Animal
  • Female
  • Gait
  • Heterozygote
  • Male
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Phenotype
  • Potassium Channels / genetics*
  • Purkinje Cells / pathology*
  • Rats
  • Rats, Inbred WF
  • Rats, Mutant Strains / genetics*
  • Rats, Sprague-Dawley
  • Shaker Superfamily of Potassium Channels
  • Tremor / genetics
  • Tremor / pathology
  • Tremor / physiopathology
  • X Chromosome*

Substances

  • Potassium Channels
  • Shaker Superfamily of Potassium Channels