title: Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: an animal model of human Brody disease.
abstract: Congenital pseudomyotonia in Chianina cattle is a muscle function disorder very similar to that of Brody disease in humans. Mutations in the human ATP2A1 gene, encoding SERCA1, cause Brody myopathy. The analysis of the collected Chianina pedigree data suggested monogenic autosomal recessive inheritance and revealed that all 17 affected individuals traced back to a single founder. A deficiency of SERCA1 function in skeletal muscle of pseudomyotonia affected Chianina cattle was observed as SERCA1 activity in affected animals was decreased by about 70%. Linkage analysis showed that the mutation was located in the ATP2A1 gene region on BTA25 and subsequent mutation analysis of the ATP2A1 exons revealed a perfectly associated missense mutation in exon 6 (c.491G>A) leading to a p.Arg164His substitution. Arg164 represents a functionally important and strongly conserved residue of SERCA1. This study provides a suitable large animal model for human Brody disease.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Berne, Bremgartenstrasse 109a, CH-3001 Berne, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Michaela
authors.initials: M
authors.lastname: Drögemüller
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.forename: Francesco
authors.initials: F
authors.lastname: Mascarello
authors.forename: Stefania
authors.initials: S
authors.lastname: Testoni
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Gentile
authors.forename: Ernesto
authors.initials: E
authors.lastname: Damiani
authors.forename: Roberta
authors.initials: R
authors.lastname: Sacchetto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics; D002417:Cattle / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020386:Isaacs Syndrome / Q000151:congenital / Q000235:genetics / Q000662:veterinary*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009224:Myotonia Congenita / Q000235:genetics*; D010375:Pedigree; D010805:Physical Conditioning, Animal; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*
chemical_list: D001120:Arginine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases