title: Intragenic deletion in the gene encoding L-gulonolactone oxidase causes vitamin C deficiency in pigs.
abstract: The absence of L-ascorbic acid (L-AA, or AA) synthesis in scurvy-prone organisms, including humans, other primates, guinea pigs, and flying mammals, was traced to the lack of L-gulonolactone oxidase (GULO) activity. GULO is a microsomal enzyme that catalyzes the terminal step in the biosynthesis of L-AA. Clinical cases of scurvy were described in a family of Danish pigs. This trait is controlled by a single autosomal recessive allele designated od (osteogenic disorder). Here we demonstrate that the absence of GULO activity and the associated vitamin C deficiency in od/od pigs is due to the occurrence of a 4.2-kbp deletion in the GULO gene. This deletion includes 77 bp of exon VIII, 398 bp of intron 7 and 3.7 kbp of intron 8, which leads to a frame shift. The mutant protein is truncated to 356 amino acids, but only the first 236 amino acids are identical to the wild-type GULO protein. In addition, the od allele seems to be less expressed in deficient and heterozygous pigs compared with the normal allele in heterozygous and wild-type animals as determined by ribonuclease protection assay. We also developed a DNA-based test for the diagnosis of the deficient allele. However, we failed to identify the mutated allele in other pig populations.
authors.affiliation: Institute of Animal Sciences, Tannenstrasse 1, ETH-Zentrum, CH-8092 Zurich, Switzerland.
authors.forename: Lara
authors.initials: L
authors.lastname: Hasan
authors.forename: Peter
authors.initials: P
authors.lastname: Vögeli
authors.forename: Peter
authors.initials: P
authors.lastname: Stoll
authors.forename: Spela Spilar
authors.initials: SS
authors.lastname: Kramer
authors.forename: Gerald
authors.initials: G
authors.lastname: Stranzinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Neuenschwander
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000097:blood*; D001206:Ascorbic Acid Deficiency / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern / Q000662:veterinary; D003433:Crosses, Genetic; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D050544:L-Gulonolactone Oxidase; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D013552:Swine / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D004247:DNA; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid