These α1(Q266I) mice contain the amino acid mutation Q266I in exon 7 of the glycine receptor, alpha 1 subunit (Glra1) gene. Heterozygotes are viable and fertile. Homozygotes die at about 2-3 weeks of age (or should be sacrificed for humane reasons). Glycine receptors are ligand-gated chloride channels found in the brain stem, spinal cord, hippocampus, cerebellum, nucleus accumbens, and olfactory bulb where they mediate inhibitory neurotransmissions. Their inhibitory function is enhanced by alcohols and volatile anesthetics. In humans, disruption of the receptor has been linked to Hyperekplexia (aka Stiff person syndrome), neonatal apnea, excessive movement during sleep, brain damage, epilepsy, a head-retraction reflex and cases of Sudden Infant Death. This strain contains a Q266I mutation in the in transmembrane domain 2, which reduces glycine receptor sensitivity and eliminates ethanol potentiation of the receptor. These mice exhibit increased startle response, increased sensitivity to strychnine and pentylenetetrazole induced seizures, muscle tremors, motor control abnormalities, and reduced body weight. They also display severely decreased receptor response to isoflurane and chloroform. They show increased duration of the loss of righting reflex after injection with ketamine, and flurazepam. These mice may be useful for studying glycine receptor sensitivity to alcohols and volatile anesthetics.
