Masson Stewart W C, Cutler Harry B, James David E
School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
EMBO J. 2024 Nov;43(21):4814-4821. doi: 10.1038/s44318-024-00221-2. Epub 2024 Sep 16.
Metabolic diseases are caused by a complex interplay between genetics and the environment, yet many basic studies guiding our understanding of metabolism are confined to single genetic backgrounds, like the C57BL/6 J mouse. Recent studies across different genetic backgrounds have revealed profound phenotypic diversity, questioning the robustness and utility of observations derived from isolated strains. Those embracing genetic diversity will likely discover novel and penetrant mechanisms underlying metabolic dysregulation and disease, and findings may even benefit from increased translatability to humans. The purpose of this commentary is to equip researchers with a practical guide to performing studies across genetically diverse mice, and to highlight some of the important challenges such studies present.
代谢性疾病是由基因与环境之间复杂的相互作用引起的，然而，许多指导我们理解新陈代谢的基础研究都局限于单一的遗传背景，比如C57BL/6 J小鼠。最近针对不同遗传背景的研究揭示了深刻的表型多样性，这对源自单一品系的观察结果的稳健性和实用性提出了质疑。那些纳入遗传多样性的研究可能会发现代谢失调和疾病背后新的、具有穿透性的机制，而且研究结果甚至可能因提高了对人类的可转化性而受益。本评论的目的是为研究人员提供一份实用指南，指导他们开展针对遗传背景多样的小鼠的研究，并强调此类研究面临的一些重要挑战。
