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

  • 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.
Author:Lore Becker, Bettina Hartenstein, Johannes Schenkel, Jochen Kuhse, Heinrich BetzGND, Hans Weiher
Pubmed Id:
Parent Title (English):European journal of neuroscience
Place of publication:Oxford [u. a.]
Document Type:Article
Year of Completion:2000
Year of first Publication:2000
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/01/03
Tag:glycine receptor; hereditary hyperekplexia; spa/spa TG456 mice; startle syndrome
Page Number:6
First Page:27
Last Page:32
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
Institutes:Biowissenschaften / Biowissenschaften
Angeschlossene und kooperierende Institutionen / MPI für Hirnforschung
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0