Summary: | Hair growth and morphology are generally regulated by the hair cycle in mammals. Fibroblast Growth Factor 5 (FGF5), which is a hair cycle regulator, has a role in regulating the hair cycle during the transition from the anagen phase to the catagen phase, and a hereditary long hair phenotype has been widely reported when <i>FGF5</i> is mutated in humans and other species. However, there has been no such report in rabbits. Thus, the first exon of rabbit <i>FGF5</i> was disrupted by the CRISPR/Cas9 system, and the phenotype of <i>FGF5<sup>-/-</sup></i> rabbits was characterized while using hematoxylin and eosin (H&E) staining, immunohistochemistry, quantitative PCR, scanning electron microscopy, and western blotting. The results showed a significant and systemic long hair phenotype in the <i>FGF5<sup>-/-</sup></i> rabbits, which indicated that <i>FGF5</i> is a negative regulator of hair growth. In addition, a decreased diameter of the fiber and a higher area proportion of hair follicle clusters were determined in <i>FGF5</i><sup>-/-</sup> rabbits as compared with the WT rabbits. Further investigation verified that prolonging the anagen phase in rabbits, with decreased BMP2/4 pathway signaling and increased VERSICAN pathway signaling, caused the systemic long hair phenotype. Taken together, these results indicate a systemic long hair phenotype by prolonging anagen in <i>FGF5<sup>-/-</sup></i> rabbits, which could be widely used for Fur production and an ideal model for studying the mechanism of long hair in the future.
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