Department of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA (retired).
Trends Genet. 2021 May;37(5):444-459. doi: 10.1016/j.tig.2020.09.017. Epub 2020 Oct 20.
Human chromosome 21 (Hsa21) contains more than 500 genes, making trisomy 21 one of the most complex genetic perturbations compatible with life. The ultimate goal of Down syndrome (DS) research is to design therapies that improve quality of life for individuals with DS by understanding which subsets of Hsa21 genes contribute to DS-associated phenotypes throughout the lifetime. However, the complexity of DS pathogenesis has made developing appropriate animal models an ongoing challenge. Here, we examine lessons learned from a variety of model systems, including yeast, nematode, fruit fly, and zebrafish, and discuss emerging methods for creating murine models that better reflect the genetic basis of trisomy 21.
人类染色体 21 号（Hsa21）包含 500 多个基因，因此三体 21 号是最复杂的遗传干扰之一，在生命中是可以兼容的。唐氏综合征（DS）研究的最终目标是通过了解 Hsa21 基因的哪些亚群有助于在整个生命周期中产生与 DS 相关的表型，从而设计出改善 DS 患者生活质量的治疗方法。然而，DS 发病机制的复杂性使得开发合适的动物模型成为一个持续的挑战。在这里，我们研究了从各种模型系统中获得的经验教训，包括酵母、线虫、果蝇和斑马鱼，并讨论了创建更能反映三体 21 号遗传基础的小鼠模型的新方法。
