Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities
Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities
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DOI：
10.1093/hmg/ddm086
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发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Yu, Y. Eugene
中科院分区：
文献类型：
--
作者：
Li, Zhongyou;Yu, Tao;Yu, Y. Eugene
唐氏综合征是由人类21号染色体的基因组不平衡引起的，其主要被观察为21三体。人类21号染色体上的区域在小鼠10、16和17号染色体上的三个区域中是同线保守的。Ts 65 Dn小鼠是唐氏综合征最广泛使用的模型，其三体与小鼠16号染色体上56.5%的人21号染色体同线区相似。为了产生一个更完整的三体小鼠模型唐氏综合征，我们已经建立了一个22.9 Mb的重复跨越整个人类21号染色体同线区的小鼠16号染色体上使用Cre/loxP介导的远程染色体工程。通过荧光原位杂交和基于BAC的阵列比较基因组杂交证实了小鼠中完整重复的存在。重复间隔内基因的表达水平反映了突变小鼠的基因剂量效应。小鼠模型的心血管和胃肠道表型与唐氏综合征患者相似。这种新的小鼠模型是进一步了解唐氏综合症分子和细胞机制的强大工具。
Down syndrome is caused by a genomic imbalance of human chromosome 21 which is mainly observed as trisomy 21. The regions on human chromosome 21 are syntenically conserved in three regions on mouse chromosomes 10, 16 and 17. Ts65Dn mice, the most widely used model for Down syndrome, are trisomic for similar to 56.5% of the human chromosome 21 syntenic region on mouse chromosome 16. To generate a more complete trisomic mouse model of Down syndrome, we have established a 22.9 Mb duplication spanning the entire human chromosome 21 syntenic region on mouse chromosome 16 in mice using Cre/loxP-mediated long-range chromosome engineering. The presence of the intact duplication in mice was confirmed by fluorescent in situ hybridization and BAC-based array comparative genomic hybridization. The expression levels of the genes within the duplication interval reflect gene-dosage effects in the mutant mice. The cardiovascular and gastrointestinal phenotypes of the mouse model were similar to those of patients with Down syndrome. This new mouse model represents a powerful tool to further understand the molecular and cellular mechanisms of Down syndrome.