EXPRESSION IN TRANSGENIC MICE OF THE LARGE T-ANTIGEN OF POLYOMAVIRUS INDUCES SERTOLI-CELL TUMORS AND ALLOWS THE ESTABLISHMENT OF DIFFERENTIATED CELL-LINES

The large T antigen of polyomavirus (PyLT) efficiently immortalizes ro dent fibroblasts, but, unlike SV40 T antigen, it is not sufficient to achieve complete oncogenic transformation. We analysed a series of tra nsgenic mouse families that express the PyLT protein under control of the viral enhancer-promoter region. In all of them, the transgene was expressed in the seminiferous epithelium of the testis (Sertoli and ge rm cells), with no pathological consequences during most of the animal s' lives. However, every old male developed large bilateral tumours of the testes, generated by the proliferation of Sertoli cell derivative s. Cell lines could be readily established both from the tumours and f rom the still apparently normal testis before the onset of tumoral gro wth. They retained in vitro morphological and ultrastructural features characteristic of Sertoli cells. But, in addition to this major Serto li component, the maintenance of a cellular contingent of germinal ori gin was suggested by the expression of genes that are normally transcr ibed during the premeiotic and early meiotic stages of spermatogenesis (LDH-X, Hox1.4 and c-kit). The two cell types remained tightly associ ated, even at tate passages in culture, and could not be separated by conventional cloning procedures. This association in culture of the tw o cell types whose interaction is critical for spermatogenesis may pro vide a useful toot for its molecular analysis.