ALT: a young man in an orange vest is holding an axe in a forest

The woolly mammoth (Mammuthus primigenius) possessed a thick woolly coat and other cold-adaptive traits that enabled survival in harsh Arctic environments. Current de-extinction efforts focus on genetically modifying the closely related Asian elephant to express woolly mammoth traits. In this study, we establish a multiplex-edited mouse model with modifications in genes associated with hair morphology and lipid metabolism, enabling insights into traits involved in developing woolly hair and cold tolerance. Our optimized workflows achieved high editing efficiencies and produced genetically modified mice with simultaneous editing of up to seven different genes. Selected modifications include loss-of-function mutations in Fgf5, Tgm3, and Fam83g, among others. The resulting mice display exaggerated hair phenotypes including curly, textured coats, and golden-brown hair. This study establishes a rapid platform for testing mammoth-centric genetic variants while advancing methods for complex genetic model generation. These approaches inform de-extinction efforts and research into the genetic basis of mammalian hair development and cold adaptation. ### Competing Interest Statement The authors have filed a patent application based on the results of this work. All authors are current or former employees, or scientific advisors/consultants for Colossal Biosciences and/or Form Bio, and may hold stock and/or stock options in these companies. G.M.C. is a founder and shareholder of Colossal Biosciences and others - full disclosure for G.M.C. is available at http://arep.med.harvard.edu/gmc/tech.html.

ALT: a girl with blonde hair is eating a green jelly with a spoon

ALT: a cartoon elephant with a ponytail and a crown on its head

Many animal species have been shown to discriminate between individual humans in captive settings and may use a variety of cues to do so. Empirical evidence remains scarce for animals in the wild, how...