Mutations of the W (c-kit) gene, which encodes a transmembrane tyrosine kinase receptor, affect the development and differentiation of many types of stem cell. Most homozygous W mutant mice are sterile, due to a lack of germ cells arising during embryonic development, but one of the notable exceptions is Wf/Wf mice, which are fully fertile in both sexes. In order to elucidate the effects of the Wf mutation on spermatogenesis, postnatal spermatogenesis in Wf/Wf mice was histologically examined. The number of gonocytes at birth was significantly reduced and small portions of agametic seminiferous tubule segments were observed in mutant mice. It is suggested that this is due to a deficiency of primordial germ cells (PGC). Other than the agametic tubules, there was no evidence of reduced spermatogenesis after birth. These results indicate that the function of the W (c-kit) gene is more necessary for the development of PGC than for postnatal germ cells.
In order to define the role of Kit ligand (KL) growth factor encoded at the mouse steel (SI) locus in spermatogenesis, we have examined its production in Sertoli cells. As a measure KL growth factor bioactivity, the ability to support proliferation and maintenance of mast cells was used in co-culture with primary mouse Sertoli cells. On the sertoli cells derived from +/+ and Wv/Wv mice, +/+ mast cells proliferated and were supported for more than 2 weeks, but not W/Wv mast cells. In contrast, Sertoli cells from SId/SId mice could not support +/+ mast cell proliferation under similar conditions. The supportive effect required close-range interaction of Sertoli cells with cultured mast cells. These results indicate that Sertoli cells derived from +/+ and Wv/Wv but not SId/SId mutant mice produce biologically active KL growth factor as a membrane-bound form. The biologically active KL of Sertoli cells may also play an important role in germ cell growth and differentiation.