Disruption of thymocyte development and lymphomagenesis induced by SV4O T-antigen

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Abstract
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.