Unlocking metabolic insights with mouse genetic diversity

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. As part of EMBO Journal’s 2024 metabolism methods series, this commentary revisits the impact of genetics on metabolic studies, enabling dissection of novel mechanisms and phenotypes.