壊血病発症動物における遺伝子異常の解析

概要

論文の詳細を見る
L-Ascorbic acid is synthesized by animals and plants, and its analogues in fungi. Studies in the 1950s showed that scurvy-prone species, such as humans, other primates, and guinea pigs, do not possess L-gulono-γ-lactone oxidase, the terminal enzyme of the L-ascorbic acid biosynthetic pathway in animals. We first cloned a cDNA for this enzyme of rat, with which the isofunctinal enzymes of plants and fungi were later shown to be homologous at the gene level. Using the cDNA as a probe, its related DNA sequences of human and guinea pig were cloned and their gene structures were disclosed. Of note is the tremendous deterioration of the genes such as deletion of exons and nucleotide(s), nonconformity to the GT/AG rule at the intronexon junction, and occurrence of stop codons as well as a large number of substations at the amino acid level. In contrast, the genetic abnormality of osteogenic disorder Shionogi (ODS) rat was found to be due to a single missense mutation in the L-gulono-γ-lactone oxidase gene. Recent our study revealed that the knockout mouse deficient for senescence marker protein-30 was subject to scurvy when fed a vitamin C deficient diet. As a matter of fact, this protein was proven to be the gluconolactonase that catalyzes the penultimate step of the L-ascorbic acid biosynthetic pathway.
日本ビタミン学会の論文
2007-01-25