Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 1 rue Laurent Fries, 67404 Illkirch, France
Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.
Dis Model Mech. 2017 Oct 1;10(10):1165-1186. doi: 10.1242/dmm.029728.
Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage-sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets.
唐氏综合征是由 21 号染色体三体引起的。迄今为止，已经开发出多种具有唐氏综合征相关特征的小鼠模型，以帮助人们理解这种复杂的人类染色体疾病。这些小鼠模型对于确定基因型-表型关系以及鉴定与疾病病理生理学相关的剂量敏感基因，以及研究额外染色体对整个基因组的影响非常重要。唐氏综合征的小鼠模型也被用于测试治疗策略。在这里，我们概述了过去 15 年中致力于开发和应用用于唐氏综合征的啮齿动物模型的研究。我们还推测了该快速发展领域未来可能的研究方向。随着我们对该综合征的了解不断加深以及基因组工程技术的发展，有必要协调各方努力，使所有唐氏综合征模型都能为科学界所用，在能复制整条三体的模型中测试治疗方法，并设计新的动物模型以促进进一步发现潜在的治疗靶点。
