Present address: Abteilung für Anatomie und Zelluläre Neurobiologie, Universität Ulm, Albert-Einstein-Allee 11, 89069 Ulm, Germany.
Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β-subunit: an animal model of startle disease
Article first published online: 9 OCT 2008
European Journal of Neuroscience
Volume 12, Issue 1, pages 27–32, January 2000
How to Cite
Becker, L., Hartenstein, B., Schenkel, J., Kuhse, J., Betz, H. and Weiher, H. (2000), Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β-subunit: an animal model of startle disease. European Journal of Neuroscience, 12: 27–32. doi: 10.1046/j.1460-9568.2000.00877.x
- Issue published online: 9 OCT 2008
- Article first published online: 9 OCT 2008
- Received 16 March 1999, revised 10 August 1999, accepted 3 September 1999
- glycine receptor;
- hereditary hyperekplexia;
- spa/spa TG456 mice;
- startle syndrome
Startle disease or hereditary hyperekplexia has been shown to result from mutations in the α1-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 α or β-subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into the spastic mouse (spa/spa), a recessive mutant carrying a transposon insertion within the GlyR β-subunit gene. In spa/spa TG456 mice, one of three strains generated with this construct, which expressed very low levels of GlyR β 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 ∼ 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.