Details

Autor(en) / Beteiligte

• Thomsen, Bo
• Horn, Per
• Panitz, Frank
• Bendixen, Emøke
• Petersen, Anette H
• Holm, Lars-Erik
• Nielsen, Vivi H
• Agerholm, Jørgen S
• Arnbjerg, Jens
• Bendixen, Christian

Titel

A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation

Ist Teil von

• Genome Research, 2006-01, Vol.16 (1), p.97-105

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2006

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.