Multiplex-edited mice recapitulate woolly mammoth hair phenotypes

作者：Rui Chen, Melissa L. Coquelin, Kanokwan Srirattana, Rafael Vilar Sampaio, Jacob Weston, Rakesh Ganji, Raphael A. Wilson, J. L. Beebe, Alba V. Ledesma, Jacob Sullivan, Yiren Qin, Jianfei Chao, James B. Papizan, Anthony Mastracci, Ketaki Bhide, Jeremy Mathews, Gregory Knox, Rorie Oglesby, Mitra Menon, Tom van der Valk, Austin Bow, Brandi L. Cantarel, Matt James, James Kehler, Love Dalén, Ben Lamm, George M. Church, Beth Shapiro, Michael E. Abrams · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.03.03.641227 · 被引用次数：8 · 研究领域：Molecular Biology Techniques and Applications、RNA Research and Splicing、Single-cell and spatial transcriptomics

SUMMARY 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 textures. 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 advances methods of rapid establishment of complex genetic models. These approaches inform de-extinction efforts and research involving the genetic basis of mammalian hair development.