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

Abstract

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. including cats (Felis catus) 7,8 , dogs (Canis lupus familiaris) 9,10 , donkeys (Equus africanus asinus) 11 , Syrian hamster (Mesocricetus auratus) 12 , domestic guinea pigs (Cavia porcellus) 13 , and even human (Homo sapiens) 14. Sheep are one of the most important wool animals. However, traditional breeding limits the genetic improvement of sheep breeding in the short term. Current results indicate that the CRISPR-Cas9 system can be successfully employed in a broad range of organisms 15-21. In the previous study, we had successfully generated FGF5-knockout heterozygous sheep using the CRISPR/ Cas9 system by direct one-step cytoplasmic injection of Cas9 mRNA and sgRNA into zygotes, and the relationship

Phytochemical Constitution, Anti-Inflammation, Anti-Androgen, and Hair Growth-Promoting Potential of Shallot (Allium ascalonicum L.) Extract

“…Moreover, this pathway mediates the initiation and maintenance of the anagen phase [ 9 ]. It has been proposed that there might be crosstalk between the Wnt/β-catenin and androgen pathways [ 44 ]. The differentiation of hair follicle stem cells was abolished by DHT [ 45 ].…”

“…Likewise, the sonic hedgehog signaling pathway regulates hair growth and hair follicle development [ 44 , 52 ]. It has been presumed that sonic hedgehog signaling is the downstream pathway of the Wnt/β-catenin signaling to regulate hair follicle induction [ 53 ].…”

Improvements in Gene Editing Technology Boost Its Applications in Livestock

“…More recently, farm animals with point mutations and gene insertions (KI) have been successfully produced using ssODN donor sequences, CRISPR/Cas9 base editing and CRISPR/Cas9 nickase approaches ( Table 3 ). The applications of gene editing technologies for generation of livestock are very diverse, ranging from enhancing important production traits such as meat, milk, and fiber production ( Deng et al, 2014 ; Crispo et al, 2015 ; Hu et al, 2017 ; Zhou et al, 2017 ; Zhang R. et al, 2020 ) to improving disease resistance, health, reproductive efficiency, facilitating animal welfare, and developing new biomedical models to better understand the etiology of diseases and develop novel mechanism-based therapeutic approaches ( Vilarino et al, 2017 ; Fan et al, 2018a , b ; Tu et al, 2019 ; Tanihara et al, 2020 ).…”

A 90-Day Safety Study of Meat from MSTN and FGF5 Double-Knockout Sheep in Wistar Rats

“…Furthermore, natural mutations in the FGF5 locus in cats and dogs also result in increases in their coat length [8,9]. Upon the use of genome editing technology to produce FGF5-KO goats and sheep, both groups of animals exhibited increased hair length and density [10,11]. In summary, mutating the MSTN and FGF5 genes can increase the economic value of large agricultural animals.…”