A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons

Abstract

The testis-specific protein Y-encoded (TSPY) gene is a candidate for the gonadoblastoma locus on the Y chromosome and is expressed in normal testicular germ cells and gonadoblastoma cells of XY sex-reversed females. Although TSPY expression has been demonstrated in gonadoblastoma tissues, it is uncertain if such expression is involved in a causative or consequential event of the oncogenic process. We postulate that if TSPY is involved in gonadoblastoma development, its promoter should be functional in the female gonad before and/or at early stages of tumorigenesis. To test this hypothesis, we generated several lines of transgenic mice harboring a Cre-recombinase transgene directed by a 2.4-kb hTSPY promoter. These mice were crossed with the Z/EG reporter line that expresses EGFP only after a Cre-mediated recombination. Our results showed that hTSPY-Cre;Z/EG double transgenic mice expressed EGFP specifically in the germ cells of both male and female gonads. Further, neurons of the central and peripheral nervous systems also expressed EGFP as early as E12.5 embryonic stage. EGFP was particularly observed in the trigeminal nerve, trigeminal ganglion, dorsal root of the ganglia, and in postnatal and adult brains. These observations support the hypothesis that TSPY plays an active role in gonadoblastoma. The tissue-specific expression of the hTSPY-Cre transgene should also be useful in studies utilizing Cre-mediated gene activation/inactivation strategies in gamatogenesis and/or neurogenesis.