Cover Image

Disease-specific human glycine receptor α [alpha]1 subunit causes hyperekplexia phenotype and impaired glycine- and GABA(A)-receptor transmission in transgenic mice

Hereditary hyperekplexia is caused by disinhibition of motoneurons resulting from mutations in the ionotropic receptor for the inhibitory neurotransmitter glycine (GlyR). To study the pathomechanisms involved in vivo, we generated and analyzed transgenic mice expressing the hyperekplexia-specific do...

Full description

Saved in:
Bibliographic Details
Main Authors: Becker, Lore (Author) , Wegerer, Jörg (Author) , Schenkel, Johannes (Author) , Zeilhofer, Hanns Ulrich (Author) , Swandulla, Dieter (Author) , Weiher, Hans (Author)
Format: Article (Journal)
Language:English
Published: 1 April 2002
In: The journal of neuroscience
Year: 2002, Volume: 22, Issue: 7, Pages: 2505-2512
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.22-07-02505.2002
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1523/JNEUROSCI.22-07-02505.2002
Get full text
Author Notes:Lore Becker, Jörg von Wegerer, Johannes Schenkel, Hanns-Ulrich Zeilhofer, Dieter Swandulla, and Hans Weiher
Description
Summary:Hereditary hyperekplexia is caused by disinhibition of motoneurons resulting from mutations in the ionotropic receptor for the inhibitory neurotransmitter glycine (GlyR). To study the pathomechanisms involved in vivo, we generated and analyzed transgenic mice expressing the hyperekplexia-specific dominant mutant human GlyR alpha1 subunit 271Q. Tg271Q transgenic mice, in contrast to transgenic animals expressing a wild-type human alpha1 subunit (tg271R), display a dramatic phenotype similar to spontaneous and engineered mouse mutations expressing reduced levels of GlyR. Electrophysiological analysis in the ventral horn of the spinal cord of tg271Q mice revealed a diminished GlyR transmission. Intriguingly, an even larger reduction was found for GABA(A)-receptor-mediated inhibitory transmission, indicating that the expression of this disease gene not only affects the glycinergic system but also leads to a drastic downregulation of the entire postsynaptic inhibition. Therefore, the transgenic mice generated here provide a new animal model of systemic receptor interaction to study inherited and acquired neuromotor deficiencies at different functional levels and to develop novel therapeutic concepts for these diseases.
Item Description:Im Text ist alpha als griechischer Buchstabe dargestellt
Im Text sind die 1 und das A nach GABA tiefgestellt
Gesehen am 07.10.2020
Physical Description:Online Resource
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.22-07-02505.2002

Similar Items