Abstract
The mutant mouse spastic, which carries a single-locus, recessive mutation1 on chromosome 3 (refs 2, 3), is characterized by hyperexcitability, rapid tremor, rigidity and prolonged righting reflexes1. No anatomical abnormalities have been found in preliminary histological studies of muscle or the central nervous system (CNS)1. Electromyographic studies in spastic mice demonstrate abnormal electrical bursts during activity and abnormal stereotyped reflexes4. Drugs which increase γ-aminobutyric acid (GABA)5 or enhance GABA synaptic action6 reduce spastic symptoms, suggesting that they result from an imbalance in excitatory and inhibitory influences in the spastic CNS. Strychnine antagonizes the synaptic action of glycine7, and binds to a membrane site with the characteristics of the postsynaptic glycine receptor8–11. The behavioural and electrophysiological abnormalities of spastic mice are reproduced in normal mice given subconvulsive doses of strychnine4, suggesting that spastic symptoms might result from a deficiency in glycine-mediated inhibition4. We describe here evidence that supports this hypothesis: a decrease in 3H-strychnine binding in membrane fractions prepared from spastic compared with littermate control mice. We also demonstrate an involvement of the benzodiazepine, and possibly the GABA, binding site in the spastic phenotype.
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White, W., Heller, A. Glycine receptor alteration in the mutant mouse spastic. Nature 298, 655–657 (1982). https://doi.org/10.1038/298655a0
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DOI: https://doi.org/10.1038/298655a0
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