氧化还原酶DHTKD1基因突变致病机制及小鼠模型研究进展  

Research Progress on Pathogenesis of Hereditary Diseases Caused by Mutations of Oxidoreductase DHTKD1 and Related Mouse Models

作　　者：沈艳 徐汪洋[1] 朱后保 SHEN Yan;XU Wang-yang;ZHU Hou-bao(Research Center for Experimental Medicine of Rui-Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院实验医学研究中心,上海200025

出　　处：《实验动物与比较医学》2018年第6期468-472,共5页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金(81201365和81502048)

摘　　要：氧化还原酶,脱氢酶E1和转酮酶结构域1(DHTKD1)通过催化2-酮己二酸氧化脱氢生成戊二酰辅酶A,终产物乙酰辅酶A进入三羧酸循环,产生三磷酸腺苷(ATP)为细胞机体提供能量。迄今为止,研究显示,DHTKD1基因多个位点的突变与线粒体功能障碍有关,最终导致人类遗传疾病的发生。本文重点阐述了DHTKD1基因突变与人类遗传病的相关性及其相应的机制,并对已有的2种基因敲除小鼠模型进行了比较探讨。As an oxidoreductase,dehydrogenase E1 and transketolase domain-containing 1(DHTKD1)catalyzes the oxidation dehydrogenation of 2-ketoadipic acid to produce glutaryl-CoA.Then the final product,acetyl-CoA enters the tricarboxylic acid cycle,finally producing adenosine-triphosphate(ATP)to provide energy for the cell and organism.So far,researchers have found that mutations in multiple loci of DHTKD1 gene are associated with mitochondrial dysfunction,leading to genetic diseases in human.This article focuses on the correlation between DHTKD1 gene mutation and human genetic diseases,and discussion about the corresponding mechanism.Furthermore,we dialectically discuss two available knockout mouse models.

关 键 词：脱氢酶E1和转酮酶结构域1(DHTKD1)基因 基因突变 遗传病 线粒体 小鼠模型 

分 类 号：Q95-33[生物学—动物学]