唐氏综合征小鼠模型的遗传背景和应用

doi:10.16288/j.yczz.17-279

遗传 ›› 2018, Vol. 40 ›› Issue (3): 207-217.doi: 10.16288/j.yczz.17-279

唐氏综合征小鼠模型的遗传背景和应用

孟晓伟¹,汪洁^1,²,马晴雯^1,²()

^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

收稿日期:2017-08-22 修回日期:2017-12-05 出版日期:2018-03-20 发布日期:2018-01-29
基金资助:
国家重点研发计划项目(编号：2016YFC1000503)

The genetic background and application of Down syndrome mouse models

Xiaowei Meng¹,Jie Wang^1,²,Qingwen Ma^1,²()

^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;

Received:2017-08-22 Revised:2017-12-05 Online:2018-03-20 Published:2018-01-29
Supported by:
[Supported by the National Key Research and Development Program of China (No. 2016YFC1000503)]

摘要/Abstract

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

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 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 associated phenotypes. In this review, we briefly introduce the different DS mouse models and discuss their advantages and limitations by focusing on the triplication of Hsa21 orthologs and manifestations of DS phenotypes, thereby providing some references for the selection of specific mouse models in DS research.

Key words: Down syndrome, mouse models, gene duplication, phenotype simulation

孟晓伟, 汪洁, 马晴雯. 唐氏综合征小鼠模型的遗传背景和应用[J]. 遗传, 2018, 40(3): 207-217.

Xiaowei Meng, Jie Wang, Qingwen Ma. The genetic background and application of Down syndrome mouse models[J]. Hereditas(Beijing), 2018, 40(3): 207-217.

参考文献

[1]	Down JL . Observations on an ethnic classification of idiots 1866. Ment Retard, 1995,33(1):54-56.
[2]	Lejeune J, Gautier M, Turpin R . Study of somatic chromosomes from 9 mongoloid children. C R Hebd Seances Acad Sci, 1959,248(11):1721-1722.
[3]	Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW . Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. J Pediatr, 1989,114(1):79-86.
[4]	Head E, Lott IT, Wilcock DM, Lemere CA . Aging in Down syndrome and the development of Alzheimer’s disease neuropathology. Curr Alzheimer Res, 2016,13(1):18-29.
[5]	Mazurek D, Wyka J . Down syndrome-genetic and nutritional aspects of accompanying disorders. Rocz Panstw Zakl Hig, 2015,66(3):189-194.
[6]	Rogers MA, Langbein L, Praetzel-Wunder S, Winter H, Schweizer J . Human hair keratin-associated proteins (KAPs). Int Rev Cytol, 2006,251:209-263.
[7]	Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Shibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Sch?n O, Desario A, Reichelt J, Kauer G, Bl?cker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML . The DNA sequence of human chromosome 21. Nature, 2000,405(6784):311-319.
[8]	Sturgeon X, Gardiner KJ . Transcript catalogs of human chromosome 21 and orthologous chimpanzee and mouse regions. Mamm Genome, 2011,22(5-6):261-271.
[9]	Gupta M, Dhanasekaran AR, Gardiner KJ . Mouse models of Down syndrome: gene content and consequences. Mamm Genome, 2016,27(11-12):538-555.
[10]	Bera TK, Zimonjic DB, Popescu NC, Sathyanarayana BK, Kumar V, Lee B, Pastan I . POTE, a highly homologous gene family located on numerous chromosomes and expressed in prostate, ovary, testis, placenta, and prostate cancer. Proc Natl Acad Sci USA, 2002,99(26):16975-16980.
[11]	Kido S, Sakuragi N, Bronner MP, Sayegh R, Berger R, Patterson D, Strauss JF . D21S418E identifies a cAMP- regulated gene located on chromosome 21q22.3 that is expressed in placental syncytiotrophoblast and choriocarcinoma cells. Genomics, 1993,17(1):256-259.
[12]	Davisson MT, Schmidt C, Akeson EC . Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog Clin Biol Res, 1990,360:263-280.
[13]	Sago H,

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

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

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 14

编辑推荐

Metrics