CRISPR/Cas9-mediated Disruption of Fibroblast Growth Factor 5 in Rabbits Results in a Systemic Long Hair Phenotype by Prolonging Anagen

• Main Authors: Yuxin Xu, Hongmei Liu, Huilin Pan, Xinyue Wang, Yuxin Zhang, Bing Yao, Nannan Li, Liangxue Lai, Zhanjun Li
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Genes
• Subjects: fgf5; rabbit; hair cycle; long hair
• Online Access: https://www.mdpi.com/2073-4425/11/3/297

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^-/-</i> rabbits was characterized while using hematoxylin and eosin (H&amp;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^-/-</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>^-/- 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^-/-</i> rabbits, which could be widely used for Fur production and an ideal model for studying the mechanism of long hair in the future.