The study investigates the role of Plzf in adult male germ cell self-renewal. The classical mouse mutant luxoid, which affects adult germline stem cell self-renewal, is characterized by limited production of normal spermatozoa followed by progressive loss of germ cells after birth. Transplantation experiments show that germ cells from luxoid mutant mice do not colonize recipient testes, indicating an intrinsic defect in the stem cells. The luxoid mutation is found to be a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells. Plzf is coexpressed with Oct4 in undifferentiated spermatogonia, suggesting its importance in maintaining the undifferentiated state of stem cells. The study provides evidence that Plzf is essential for stem cell self-renewal in mammals, particularly in the context of adult male germ cells.The study investigates the role of Plzf in adult male germ cell self-renewal. The classical mouse mutant luxoid, which affects adult germline stem cell self-renewal, is characterized by limited production of normal spermatozoa followed by progressive loss of germ cells after birth. Transplantation experiments show that germ cells from luxoid mutant mice do not colonize recipient testes, indicating an intrinsic defect in the stem cells. The luxoid mutation is found to be a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells. Plzf is coexpressed with Oct4 in undifferentiated spermatogonia, suggesting its importance in maintaining the undifferentiated state of stem cells. The study provides evidence that Plzf is essential for stem cell self-renewal in mammals, particularly in the context of adult male germ cells.