title: A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation.
abstract: The extensive use of a limited number of elite bulls in cattle breeding can lead to rapid spread of recessively inherited disorders. A recent example is the globally distributed syndrome Complex Vertebral Malformation (CVM), which is characterized by misshapen and fused vertebrae around the cervico-thoracic junction. Here, we show that CVM is caused by a mutation in the Golgi-resident nucleotide-sugar transporter encoded by SLC35A3. Thus, the disease showed complete cosegregation with the mutation in a homozygous state, and proteome patterns indicated abnormal protein glycosylation in tissues of affected animals. In addition, a yeast mutant that is deficient in the transport of UDP-N-acetylglucosamine into its Golgi lumen can be rescued by the wild-type SLC35A3 gene, but not by the mutated gene. These results provide the first demonstration of a genetic disorder associated with a defective SLC35A3 gene, and reveal a new mechanism for malformation of the vertebral column caused by abnormal nucleotide-sugar transport into the Golgi apparatus.
authors.affiliation: Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, DK-8830 Tjele, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Thomsen
authors.forename: Per
authors.initials: P
authors.lastname: Horn
authors.forename: Frank
authors.initials: F
authors.lastname: Panitz
authors.forename: Emøke
authors.initials: E
authors.lastname: Bendixen
authors.forename: Anette H
authors.initials: AH
authors.lastname: Petersen
authors.forename: Lars-Erik
authors.initials: LE
authors.lastname: Holm
authors.forename: Vivi H
authors.initials: VH
authors.lastname: Nielsen
authors.forename: Jørgen S
authors.initials: JS
authors.lastname: Agerholm
authors.forename: Jens
authors.initials: J
authors.lastname: Arnbjerg
authors.forename: Christian
authors.initials: C
authors.lastname: Bendixen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D002417:Cattle / Q000002:abnormalities* / Q000235:genetics; D002418:Cattle Diseases / Q000235:genetics; D002574:Cervical Vertebrae / Q000002:abnormalities*; D006031:Glycosylation; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009139:Musculoskeletal Abnormalities / Q000235:genetics*; D020125:Mutation, Missense; D046188:Protein Modification, Translational / Q000235:genetics*; D013904:Thoracic Vertebrae / Q000002:abnormalities*; D015003:Yeasts / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C121945:UDP-N-acetylglucosamine transporter