摘要
I型遗传性酪氨酸血症(hereditary tyrosinemia type 1,HT1)是一种常染色体隐形遗传病,主要是由于FAH基因(fumarylacetoacetate hydroxylase,FAH)突变导致酪氨酸代谢发生障碍,不能正常代谢延胡索酸和乙酰乙酸。临床上主要表现为严重的肝、肾损伤,甚至肝癌。依赖基因编辑技术的发展,Fah基因修饰的小鼠、大鼠、兔和小型猪模型均相继成功制备。目前,这些动物模型已经广泛应用于人类HT1疾病的病理生理、肝脏生物学、肝干细胞以及肝癌基因治疗的研究,同时也用于制备人源化肝和人肝细胞扩增的生物反应器。本文拟对I型遗传性酪氨酸血症动物模型的相关研究进展进行综述和探讨,为更好的研究该疾病提供一些线索。
Hereditary tyrosinemia Ⅰ(HT Ⅰ)is an autosomal recessive disease characterized by progressive liver and kidney damage with a high risk of hepatocellular carcinoma.HT Ⅰ is caused by mutations of the gene encoding fumarylacetoacetate hydrolase(FAH),the last enzyme in the tyrosine catabolic pathway.Several animal models of Fah deficiency have been established,including mouse,rats,rabbits,and pigs,using a recently developed gene-modifying technique.These animal models have become important for liver biology research and are widely used in liver stem cell and hepatic gene therapy studies.Furthermore,Fah mutants can be used as a bioreactor for the expansion of hepatocytes.These chimeric animals have become valuable models for basic research of infectious diseases,metabolism,and gene therapy.Here,we review the progress of animal models of HT I and their applications.
作者
顾鹏
刘闻
袁进
徐名衬
陈傍柱
徐涛
顾为望
GU Peng;LIU Wen;YUAN Jin;XU Mingchen;CHEN Bangzhu;XU Tao;GU Weiwang(Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China;Songshan Lake Pearl Laboratory Animal Science and Technology Co. Ltd. , Dongguan 523808)
出处
《中国比较医学杂志》
CAS
北大核心
2018年第12期119-123,共5页
Chinese Journal of Comparative Medicine
基金
广州市科技计划项目(201704020012)
国际科技合作项目(2011DFA33290)
广东省科技计划项目(2010A011200003
2012B011000004)
作者简介
顾鹏(1993—),男,硕士研究生,研究方向:基因修饰小型猪模型的研究。E-mail: gerogegu@ hotmail.com;通信作者:顾为望(1956—),男,教授,博士生导师,研究方向:实验动物培育、人类疾病动物模型制备与比较医学,E-mail: Guww100@163.com
