Longitudinal neuroanatomical and behavioral analyses show phenotypic drift and variability in the Ts65Dn mouse model of Down syndrome.
Longitudinal neuroanatomical and behavioral analyses show phenotypic drift and variability in the Ts65Dn mouse model of Down syndrome.
复制标题
DOI：
10.1242/dmm.046243
复制
发表时间：
2020-09-25
影响因子：
4.3
通讯作者：
Haydar TF
中科院分区：
文献类型：
--
作者：
Shaw PR;Klein JA;Aziz NM;Haydar TF
唐氏综合症 (DS) 小鼠模型已成为增进了解唐氏综合症患者智力障碍潜在机制的宝贵工具。 Ts(1716)65Dn (Ts65Dn) 小鼠是最常用的模型之一，因为它概括了 DS 个体中观察到的许多表型，包括神经解剖学变化以及学习和记忆受损。在这项研究中，我们使用严格的指标来评估从 2014 年至今的多个 Ts65Dn 队列，包括从 2010 年首次创建群体后十代内冷冻的胚胎中恢复的一组动物。通过量化产前和产后大脑发育以及多项行为任务，我们的结果提供了 Ts65Dn 随时间的全面比较，并显示了队列之间以及不同群体之间的显着变异性。 在队列内。 Ts65Dn 小鼠中不一致的表型突出了使用该模型的具体注意事项和警告。我们概述了确保在未来研究中负责任地使用 Ts65Dn 的重要步骤。摘要：对唐氏综合症 Ts65Dn 小鼠模型时间组的比较分析揭示了影响神经发育以及学习和记忆行为的表型变异，使人们对该模型的有效性提出质疑。
Mouse models of Down syndrome (DS) have been invaluable tools for advancing knowledge of the underlying mechanisms of intellectual disability in people with DS. The Ts(1716)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with DS, including neuroanatomical changes and impaired learning and memory. In this study, we use rigorous metrics to evaluate multiple cohorts of Ts65Dn ranging from 2014 to the present, including a stock of animals recovered from embryos frozen within ten generations after the colony was first created in 2010. Through quantification of prenatal and postnatal brain development and several behavioral tasks, our results provide a comprehensive comparison of Ts65Dn across time and show a significant amount of variability both across cohorts as well as within cohorts. The inconsistent phenotypes in Ts65Dn mice highlight specific cautions and caveats for use of this model. We outline important steps for ensuring responsible use of Ts65Dn in future research. Summary: Comparative analyses of temporal cohorts of the Ts65Dn mouse model of Down syndrome reveal phenotypic variability affecting neurodevelopment and learning and memory behaviors, calling into question the validity of this model.