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Letter

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

¹ Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, DK-8830 Tjele, Denmark ² Department of Animal Health, Welfare and Nutrition, Danish Institute of Agricultural Sciences, DK-8830 Tjele, Denmark ³ Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, Denmark ⁴ Department of Radiology, Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, Denmark

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.

⁵ Corresponding author.
E-mail christian.bendixen{at}agrsci.dk; fax 45-89991300.

[The sequence data from this study has been submitted to GenBank under accession no. AY160683 [GenBank] . The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: C.B. Hirschberg, C. Abeijon, and P.J. de Jong.]

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