TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Becker, Lore
A1  - Wegerer, Jorg von
A1  - Schenkel, Johannes
A1  - Zeilhofer, Hanns-Ulrich
A1  - Swandulla, Dieter
A1  - Weiher, Hans
T1  - Disease-specific human glycine receptor alpha1 subunit causes hyperekplexia phenotype and impaired glycine- and GABA(A)-receptor transmission in transgenic mice
JF  - J Neurosci. (The Journal of Neuroscience)
N2  - 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.
Y1  - 2002
SN  - 0270-6474
SS  - 0270-6474
U6  - https://doi.org/10.1523/JNEUROSCI.22-07-02505.2002
DO  - https://doi.org/10.1523/JNEUROSCI.22-07-02505.2002
PM  - 11923415
VL  - 22
IS  - 7
SP  - 2505
EP  - 2512
PB  - Society for Neuroscience
ER  -