Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions.
Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions.
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针对所有人类染色体21直系同源区域的唐氏综合症小鼠模型的涂层有效产生和分析。
DOI：
10.3390/genes12081215
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发表时间：
2021-08-06
期刊：
影响因子：
3.5
通讯作者：
Yu YE
中科院分区：
文献类型：
--
作者：
Li Y;Xing Z;Yu T;Pao A;Daadi M;Yu YE
唐氏综合症（DS）是人类最复杂的遗传性疾病之一，也是发育迟缓和智力残疾的主要遗传原因。由于人类21号染色体（Hsa21）在小鼠基因组中的三个区域同源保守，因此小鼠仍然是DS研究中必不可少的模式生物。最近的研究表明，不同的三倍基因组区域和Hsa21基因同源物之间的复杂相互作用是主要的DS表型的基础。由于我们不能确切地知道哪些三倍复制的基因在这种特定表型的相互作用中是不可或缺的，因此希望所有进化上保守的Hsa21基因同源物在一个完整的模型中都是三倍复制的。因此，Dp(10)1Yey/+, Dp(16)1Yey/+；Dp(17)1Yey/+小鼠是反映基因剂量效应最完整的DS模型，因为它是唯一在所有Hsa21同源区域重复三倍的突变体。最近，一些团体表达了他们的担忧，他们担心产生三重化合物模型所需的努力将是如此巨大，以至于利用其独特的优势可能是不切实际的。为了减轻这些担忧，我们开发了一种策略，在目标毛色的帮助下大幅提高生成三重化合物模型的效率，结果证实，通过这种方法生成的突变小鼠表现出认知缺陷。
Down syndrome (DS) is one of the most complex genetic disorders in humans and a leading genetic cause of developmental delays and intellectual disabilities. The mouse remains an essential model organism in DS research because human chromosome 21 (Hsa21) is orthologously conserved with three regions in the mouse genome. Recent studies have revealed complex interactions among different triplicated genomic regions and Hsa21 gene orthologs that underlie major DS phenotypes. Because we do not know conclusively which triplicated genes are indispensable in such interactions for a specific phenotype, it is desirable that all evolutionarily conserved Hsa21 gene orthologs are triplicated in a complete model. For this reason, the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ mouse is the most complete model of DS to reflect gene dosage effects because it is the only mutant triplicated for all Hsa21 orthologous regions. Recently, several groups have expressed concerns that efforts needed to generate the triple compound model would be so overwhelming that it may be impractical to take advantage of its unique strength. To alleviate these concerns, we developed a strategy to drastically improve the efficiency of generating the triple compound model with the aid of a targeted coat color, and the results confirmed that the mutant mice generated via this approach exhibited cognitive deficits.
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DOI：
10.1523/jneurosci.0893-12.2012
发表时间：
2012-08-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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DOI：
10.1007/s00335-016-9661-8
发表时间：
2016-12
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
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作者：
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影响因子：
3.5
作者：
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通讯作者：
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