A nonsense mutation in the alpha 1 subunit of the inhibitory glycine receptor associated with bovine myoclonus

Inherited congenital myoclonus of Poll Hereford calves is an autosomal rece ssive disease characterized by hyperesthesia and myoclonic jerks of the ske letal musculature that occur both spontaneously and in response to sensory stimuli. Binding studies have previously shown that myoclonus is associated with specific loss of [H-3]strychnine-binding sites from spinal cord and b rain stem in affected calves, In order to identify the mutation responsible for myoclonus, we examined the candidate genes, glycine receptor alpha1 (G lra1) and beta (Glrb) subunits, in affected and normal cattle, A nonsense m utation was found at amino acid 24, located in exon 2 of the Glra1 gene in both cDNA and genomic sequences from affected but not control animals, Immu nohistochemistry, with a monoclonal antibody to alpha and beta subunits of the glycine receptor, revealed a loss of cell surface immunoreactivity in m yoclonic animals, suggesting a failure in the assembly of the receptor that could explain the characteristic phenotype of the disease.