Fshb Knockout Mouse Model, Two Decades Later and Into the Future

In 1997, nearly 20 years ago, we reported the phenotypes of follicle-stimulating hormone (FSH) β (Fshb) null mice. Since then, these mice have been useful for various physiological and genetic studies in reproductive and skeletal biology. In a 2009 review titled “FSHβ Knockout Mouse Model: A Decade Ago and Into the Future,” I summarized the need for and what led to the development of an FSH-deficient mouse model and its applications, including delineation of the emerging extragonadal roles of FSH in bone cells by using this genetic model. These studies opened up exciting avenues of research on osteoporosis and now extend into those on adiposity in postmenopausal women. Here, I summarize the progress made with this mouse model since 2009 with regard to FSH rerouting in vivo, deciphering the role of N-glycosylation on FSHβ, roles of FSH in somatic–germ cell interactions in gonads, and provide a road map that is anticipated to emerge in the near future. Undoubtedly, the next 10 years should be an even more exciting time to explore the fertile area of FSH biology and its implications for basic and clinical reproductive physiology research.