title: A nonsense mutation in the alpha1 subunit of the inhibitory glycine receptor associated with bovine myoclonus.
abstract: Inherited congenital myoclonus of Poll Hereford calves is an autosomal recessive disease characterized by hyperesthesia and myoclonic jerks of the skeletal musculature that occur both spontaneously and in response to sensory stimuli. Binding studies have previously shown that myoclonus is associated with specific loss of [(3)H]strychnine-binding sites from spinal cord and brain stem in affected calves. In order to identify the mutation responsible for myoclonus, we examined the candidate genes, glycine receptor alpha1 (Glra1) and beta (Glrb) subunits, in affected and normal cattle. A nonsense mutation 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. Immunohistochemistry, with a monoclonal antibody to alpha and beta subunits of the glycine receptor, revealed a loss of cell surface immunoreactivity in myoclonic animals, suggesting a failure in the assembly of the receptor that could explain the characteristic phenotype of the disease.
authors.affiliation: Neurobiology Program, Garvan Institute of Medical Research, Sydney, New South Wales, 2010, Australia.
authors.forename: K D
authors.initials: KD
authors.lastname: Pierce
authors.forename: C A
authors.initials: CA
authors.lastname: Handford
authors.forename: R
authors.initials: R
authors.lastname: Morris
authors.forename: B
authors.initials: B
authors.lastname: Vafa
authors.forename: J A
authors.initials: JA
authors.lastname: Dennis
authors.forename: P J
authors.initials: PJ
authors.lastname: Healy
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001923:Brain Chemistry; D002417:Cattle; D003001:Cloning, Molecular; D018389:Codon, Nonsense; D018076:DNA, Complementary; D005820:Genetic Testing; D018684:Glycine Agents / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009207:Myoclonus / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D018009:Receptors, Glycine / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D013331:Strychnine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary; D018684:Glycine Agents; D018009:Receptors, Glycine; D013331:Strychnine