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Fibroblast growth factor 5  ( FGF5 ) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of  FGF5  gene result in a longer wool in mice, donkeys, dogs, cats, and even in human eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five  FGF5 -knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of  FGF5  mRNA in knockout (KO) sheep decreased significantly, and all FGF5 proteins were dysfunctional. The KO sheep displayed a significant increase in fine-wool and active hair-follicle density. The crosstalk between androgen and  Wnt/β-catenin  signaling downstream of  FGF5  gene plays a key role. We established downstream signaling cascades for the first time, including  FGF5 ,  FGFR1 , androgen,  AR ,  Wnt/β-catenin ,  Shh/Gli2 ,  c-MYC , and  KRTs . These findings further improved the function of  FGF5  gene, and provided therapeutic ideas for androgen alopecia.

Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep