LOW-LEVEL EXPRESSION OF GLYCINE RECEPTOR-BETA SUBUNIT TRANSGENE IS SUFFICIENT FOR PHENOTYPE CORRECTION IN SPASTIC MICE

Mutations in inhibitory glycine receptor (GlyR) subunit genes are asso ciated with neuromotor diseases in man and mouse, To use the potential of the mouse mutants as animal models of human disease, we altered Gl yR levels in mutant mice and studied their phenotype. A transgene codi ng for the beta subunit of the rat GlyR was introduced into the geneti c background of the spa mutation, which is characterized by low endoge nous expression levels of the beta subunit and a dramatic neuromotor p henotype. The resulting transgenic mice expressed the beta subunit mRN A at intermediate levels, and their phenotype was rescued. This provid es formal proof for the causal relationship between GlyR beta gene mut ation and motor disease, and indicates that a low level of beta gene e xpression (25% of normal) is sufficient for proper functioning of glyc inergic synapses.