The inhibitory glycine receptor is a ligand-gated chloride channel that exists in developmentally regulated isoforms. These oligomeric transmembrane proteins are composed of variants of the ligand binding α subunit and structural β polypeptides. The agonist and antagonist sites of the α subunits are formed by discontinuous sequence motifs. In the murine genome, the genes encoding the α1 ( Glra1), α3 (Glra3), and β (Glyrb) subunit are autosomally located, whereas the α2 (Glra2) and α4 (Glra4) genes reside on the X-chromosome. Mutations of glycine receptor genes have been found to underly hypertonic motor disorders in mice and humans. The mouse mutants spasmodic (spd) and oscillator (spdot) carry recessive mutations of the Glra 1 gene. In the phenotypically similar mouse mutant spastic (spa), the intronic insertion of a LINE-1 transposable element into the Gyrb gene results in the aberrant splicing and a consecutive loss of glycine receptors. The human neurological disorder hyperekplexia (startle disease, stiff baby syndrome) is caused by point mutations within the α1 subunit gene (GLRA1) localized in the human chromosomal region 5q31.3. The Neuroscientist 1:130- 141,1995
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