Testicular germ cell tumors (TGCTs) are the first tumors where the cell of origin, and the time of transformation were precisely defined. TGCTs in mice originate from primordial germ cells (PGCs) and develop within the testis during fetal development. TGCTs occur at an appreciable frequency (5%) only in the 129 family of inbred strains of laboratory mice, suggesting strong genetic control. These developmental and genetic properties make the 129 strains an exceptional model system to dissect TGCT pathogenesis. Ter is one of the most potent cancer modifiers genes known; it is a single gene mutation that causes progressive loss of PGCs on all inbred strain backgrounds and dramatically increased susceptibility to spontaneous TGCTs only on the 129 background. We recently showed that inactivation of the Dead end gene causes the Ter phenotype. Sequence analysis of Dead end encoded protein indicates it is homologous to factors involved in gene editing. The identity of Ter as Dead end and its function in PGCs will help clarify the role of editing in PGC biology and elucidate the causes of TGCTs in mice and humans.
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