カンノ　ヒトシ   菅野　仁    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	総説
言語種別	日本語
査読の有無	査読なし
表題	[Molecular basis and pathophysiology of red cell enzymopathies].
掲載誌名	正式名：Nihon rinsho. Japanese journal of clinical medicine 略　 称：Nihon Rinsho ISSNコード：0047-1852(Print)0047-1852(Linking)
巻・号・頁	54(9),2382-9頁
著者・共著者	Kanno H
担当区分	筆頭著者,責任著者
発行年月	1996/09
概要	Recent progress in the molecular analysis of red cell enzymopathies showed over 160 mutations in the 10 distinct genes which were essential in red cell metabolisms. In addition, since three-dimensional structure of several enzymes including pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) have been elucidated from X-ray crystallographic studies, the effect of amino acid substitutions on enzyme activity became predictable in some extent. On the contrary, the mechanism of hemolysis remains still unclear. To clarify the pathophysiology of red cell enzymopathies, establishment of an animal model have been long awaited. Recently we discovered the novel mice model of PK deficiency. The mutant mice with splenomegaly and nonspherocytic hemolytic anemia in an inbred colony of the CBA strain were enzymatically diagnosed as PK deficiency. A homozygous missense mutation was identified in the red cell (R)-type PKcDNA sequence of the mutant, and it caused a single amino acid substitution near the substrate binding site of PK. The erythroid-progenitor cell number increased in spleen of the mutant mice to a level approximately 66 times higher than in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice might partly compensate the anemia. The mutant mice will be useful as an experimental model for understanding the pathophysiology of this disorder.
文献番号	8890566