DISRUPTION OF THYMOCYTE DEVELOPMENT AND LYMPHOMAGENESIS INDUCED BY SV40 T-ANTIGEN

The Ick gene encodes a membrane-associated protein tyrosine kinase that is expressed specifically in lymphoid cells, especially thymocytes. Structural analysis of the murine and human Ick genes previously identified conserved 5 flanking sequences that were proposed to represent transcriptional regulatory elements. Here we demonstrate that a murine Ick promoter construct containing these sequences directs the expression of the SV4O T-antigen gene in lymphoid cells. Remarkably, expression of SV4O T-antigen in transgenic animals dramatically disturbs thymic development, resulting in preferentIal loss of CD4+CD8+thymocytes. In contrast, immature cells lacking both CD4 and CD8 markers are present in near-normal numbers. Thus SV4O T-antigen expression appears partially to arrest thymopolesis. Mice bearing the Ick-SV4O transgene develop readily explantable thymic tumors at 12–18 weeks of age. Fluorocytometric analyses of Ick-SV4O tumor cells reveal that Immature thymocytes are frequently immortalized. The Ick-SV4O mouse may therefore provide materials for the in vitro investigation of thymocyte differentiation. © 1990 Oxford University Press.