Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor beta-subunit: an animal model of startle disease

Eur J Neurosci. 2000 Jan;12(1):27-32. doi: 10.1046/j.1460-9568.2000.00877.x.


Startle disease or hereditary hyperekplexia has been shown to result from mutations in the alpha1-subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss-of-function mutations of GlyR alpha or beta-subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR beta transgene into the spastic mouse (spa/spa), a recessive mutant carrying a transposon insertion within the GlyR beta-subunit gene. In spa/spa TG456 mice, one of three strains generated with this construct, which expressed very low levels of GlyR beta transgene-dependent mRNA and protein, the spastic phenotype was found to depend upon the transgene copy number. Notably, mice carrying two copies of the transgene showed an age-dependent sensitivity to tremor induction, which peaked at approximately 3-4 weeks postnatally. This closely resembles the development of symptoms in human hyperekplexia patients, where motor coordination significantly improves after adolescence. The spa/spa TG456 line thus may serve as an animal model of human startle disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Crosses, Genetic
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Hyperkinesis / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Phenotype
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Glycine / genetics*
  • Receptors, Glycine / metabolism*
  • Reflex, Startle / genetics*
  • Spinal Cord / metabolism*
  • Transcription, Genetic
  • Tremor / genetics*
  • Tremor / physiopathology


  • GLRB protein, human
  • Glrb protein, mouse
  • Glrb protein, rat
  • RNA, Messenger
  • Receptors, Glycine