Furthermore, constitutively active IMD 0354 NOTCH1 signaling in gonadal somatic cells caused dramatic Leydig cell loss, suggesting its necessity for the maintenance of Leydig progenit or cells. However, the function and necessity of Notch signaling in germ cells and Primaquine Diphosphate spermatogenesis have not yet been examined well. Some articles reported that NOTCH1 was dispensable for normal spermatogenesis from phenotypic analyses of conditional Notch1-deleted mice, and Notch family receptors and their ligands were expressed stage-specifically in germcell and testicular somatic cells. Although there are some in consistencies in regard to the localization of each Notch or thologue, spermatogonia are considered as one of the important expression sites of Notch family receptors, and NOTCH1 has some effects on germ cell development to some extent. Furthermore, mice with germ cell-specific over expression of NOTCH1 showed reduced spermatogenesis progressively affected by age. These findings suggest that Notch signaling has some functional roles in both germ cells and spermatogenesis. In this study, we will show that novel germ cell-specific gene Nkapl is a functional nuclear protein expressed robustly in differentiating spermatogonia and spermatocytes after puberty in mice and is a repressor of Notch signaling, interacting with co-repressor proteins and transcription factors. Furthermore, NKAPL affects transcription of SSC markers and differentiation through the Notch signaling pathway and is an indispensable gene for spermatogenesis. The Notch signaling pathway is essential for the regulation of cell fate during development and throughout postnatal life in self-renewing tissues. In T-cell development, NOTCH1 deficiency causes a developmental block at an early stage. However, constitutional high expression of NOTCH1 by induction of the Notch1 active domain or deletion of Nkap, a transcriptional suppressor of the Notch signaling pathway, also blocked T-cell development. These findings suggested that Notch signaling should be controlled properly to sustain T-cell development, and both constitutional activation and complete in activation of Notch signaling hamper its development.