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Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for α1 and β glycine receptor subunits
Author(s) -
Simon Ely S.
Publication year - 1997
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.870120213
Subject(s) - glycine receptor , biology , phenotype , mutant , myoclonic jerk , spasticity , genetics , gene , neuroscience , medicine , glycine , electroencephalography , amino acid , anesthesia
Impaired glycinergic inhibition causes human hyperekplexia, and may be involved in the pathogenesis of movement disorders associated with uremia, spinal cord lesions, DDT poisoning, and tetanus. Three autosomal recessive mutant mouse strains with single‐gene mutations affecting either the α1 ( spasmodic and oscillator ) or β (spastic) subunits of the glycine receptor were studied. Serial videotaped examinations assessed the severity of hyperkinetic features. Homozygote oscillator mice appeared normal until postnatal day (P) 11–14, when decreased exploratory movements, spastic gait, stimulus‐induced myoclonic bouts, rigidity, and tremor were noticeable. All symptoms gradually worsened until death by P21–P23. In contrast, spastic and spasmodic mice were most severely affected by the 3rd–5th week of life and had a lessening of symptom severity in adulthood. Within each mutant strain, there was marked interanimal variation of severity of the other motor abnormalities, possibly because of stochastic variability in developmental processes. These mutants represent good animal models for elucidation of molecular and cellular issues regarding the glycine receptor and for the study of pathogenetic mechanisms of movement disorders.