Low level expression of glycine receptor β subunit transgene is sufficient for phenotype correction in spastic mice

Abstract

Mutations in inhibitory glycine receptor (GlyR) subunit genes are associated with neuromotor diseases in man and mouse. To use the potential of the mouse mutants as animal models of human disease, we altered GlyR levels in mutant mice and studied their phenotype. A transgene coding for the β subunit of the rat GlyR was introduced into the genetic background of the spa mutation, which is characterized by low endogenous expression levels of the β subunit and a dramatic neuromotor phenotype. The resulting transgenic mice expressed the β subunit mRNA at intermediate levels, and their phenotype was rescued. This provides formal proof for the causal relationship between GlyR β gene mutation and motor disease, and indicates that a low level of β gene expression (25% of normal) is sufficient for proper functioning of glycinergic synapses.