THY-1 TK TRANSGENIC MICE WITH A CONDITIONAL LYMPHOCYTE DEFICIENCY

Thy-1 has been used as a cell surface marker for identification of mat ure T cells, T lymphoid precursors and the hematopoietic stem cell. Th e developmental program of these cells during hemato/lymphopoiesis is complex because of heterogeneity of the populations and subsequent mig ration. To study the differentiation of Thy-1 positive cells at precis e periods of in vivo development we have used a strategy based on cell specific toxicity. In the transgenic mouse studies presented here, Th y-1 positive cells are ablated by targeting the expression of the cond itional toxin Herpes simplex virus 1 thymidine kinase (tk) with Thy-1 transcriptional control elements. We demonstrate the controlled expres sion of HSV1 tk in Thy-1 expressing cells of adult transgenic mice and the conditional ablation of >90% of maturing thymocytes. We describe the distinct subpopulations of cells remaining within individual ablat ed thymuses and show by phenotypic analyses that Thy-1 tk induced abla tion enriches for CD4 low and double negative thymocytes. Furthermore, we demonstrate a differential effect of thymus directed ablation on t he maturing peripheral T cell compartment at various times in mouse de velopment. This strategy is successful for production of a conditional T lymphocyte deficiency and could be useful in the study of T lineage development and direct in vivo isolation of enriched T precursor cell populations.