唐氏综合征小鼠模型的遗传背景和应用.PDF

Hereditas (Beijing) 2018 年 3 月, 40(3): 207 ―217 综 述 唐氏综合征小鼠模型的遗传背景和应用 1 1,2 1,2 孟晓伟 ，汪洁 ，马晴雯 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 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 chromosome 21, 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/LoxP 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。 关键词 : 唐氏综合征；小鼠模型；基因重复；表型模拟 The genetic background and application of Down syndrome mouse models 1 1,2 1,2 Xiaowei Meng , Jie Wang , Qingwen Ma 1. Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China 2. Key Laboratory of Embryo Molecular Biology, Ministry of Health Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, China Abstract : Down syndrome (DS), trisomy chromosome 21 (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 Hsa21 genes 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 Hsa21 orthologs. In 2004, the successful use of the Cre/LoxP recombination technique in chromo- somal 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 an