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 utilize 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 1990. Through quantification of pre- and post-natal 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.

中文翻译：

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纵向神经解剖学和行为分析显示唐氏综合症 Ts65Dn 小鼠模型的表型漂移和变异。


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(17 ¹⁶ )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，我们利用严格的指标来评估从 2014 年至今的多个 Ts65Dn 群体，包括从 1990 年该群体首次创建后十代内冷冻胚胎中恢复的一组动物。出生时大脑发育和一些行为任务，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队列内部的显着差异。 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。