雄激素和 Wnt/β-连环蛋白之间的串扰导致 FGF5 敲除绵羊羊毛密度的变化。
Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep.
机构信息
Beijing Key Laboratory of Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Tianjin Institute of Animal Sciences, Tianjin, 300112, China.
出版信息
Cell Death Dis. 2020 May 29;11(5):407. doi: 10.1038/s41419-020-2622-x.
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.
成纤维细胞生长因子 5（FGF5）是毛发周期生长期的著名显性抑制剂。FGF5 基因突变导致老鼠、驴、狗、猫，甚至人类睫毛的毛更长。绵羊是羊毛生产的重要来源。如何快速有效地提高羊毛产量是一个亟待解决的问题。在这项研究中，我们利用 CRISPR/Cas9 系统生成了五只 FGF5 敲除的多佩罗羊。敲除（KO）绵羊中 FGF5 mRNA 的表达水平显著降低，所有 FGF5 蛋白均功能失调。KO 绵羊的细毛和活跃毛囊密度显著增加。FGF5 基因下游的雄激素和 Wnt/β-catenin 信号转导之间的串扰起着关键作用。我们首次建立了下游信号级联反应，包括 FGF5、FGFR1、雄激素、AR、Wnt/β-catenin、Shh/Gli2、c-MYC 和 KRTs。这些发现进一步提高了 FGF5 基因的功能，为雄激素性脱发提供了治疗思路。
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