唐氏综合征小鼠模型的遗传背景和应用  

The genetic background and application of Down syndrome mouse models

作　　者：孟晓伟 汪洁 马晴雯[1,2] 卢大儒 Xiaowei Meng;Jie Wang;Qingwen Ma(Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China;Key Laboratory of Embryo Molecular Biology, Ministry of Health & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, China)

机构地区：[1]上海交通大学附属儿童医院,上海市儿童医院,上海交通大学医学遗传研究所,上海200040 [2]卫生部医学胚胎分子生物学重点实验室暨上海市胚胎与生殖工程重点实验室,上海200040 [3]不详

出　　处：《遗传》2018年第3期207-217,共11页Hereditas（Beijing)

基　　金：国家重点研发计划项目(编号:2016YFC1000503)

摘　　要：唐氏综合征(Down syndrome,DS)是最常见的常染色体异常疾病,由人类21号染色体(human chromosome21,Hsa21)的重复引起。由于Hsa21的直系同源基因分散于小鼠16、17和10号染色体上,所以用小鼠模拟人类唐氏综合征并不容易。早期的Ts65Dn小鼠虽然具有DS表型特征,但其重复片段由电离辐射产生,未包含所有Hsa21直系同源基因。2004年,Cre/Lox P重组酶系统介导的染色体编辑技术在Ts1Rhr小鼠中的成功应用,解决了特定片段重复化的难题,使DS小鼠模型在基因重复和表型模拟方面实现了精准化。本文从同源基因重复和DS表型模拟两方面简要介绍了不同时期DS小鼠模型的优势和局限,为科研人员在DS研究中对不同小鼠模型的选用提供了参考。Down syndrome(DS),trisomy chromosome21(Hsa21),is the most common genetic disease caused by chromosome aberration in the human genome.Modeling DS in mice has been challenging since the orthologs of Hsa21genes map to separate segments of three mouse chromosomes,Mmu16,Mmu17,and Mmu10.Although the early Ts65Dn mouse model exhibited various DS phenotypes,the duplicated fragments were randomly generated by ionizing radiation and did not include all Hsa21orthologs.In2004,the successful use of the Cre/LoxP recombination technique in chromosomal engineering in the construction of the Ts1Rhr mouse strain solved the problem of duplication of specific chromosome segment,resulting in the establishment of specific DS mouse models with accurate triplication of particular genes and asso ciated phenotypes.In this review,we briefly introduce the different DS mouse models and discuss their advantages and limitations by focusing on the triplication of Hsa21orthologs and manifestations of DS phenotypes,thereby providing some references for the selection of specific mouse models in DS research.

关 键 词：唐氏综合征 小鼠模型 基因重复 表型模拟 

分 类 号：R-332[医药卫生] R596.1