Thy-1 tk transgenic mice with a conditional lymphocyte deficiency

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Abstract
Thy-1 has been used as a cell surface marker for identification of mature T cells, T lymphoid precursors and the hematopoietic stem cell. The developmental program of these cells during hemato/lymphopolesls is complex because of heterogeneity of the populations and subsequent migration. To study the differentiation of Thy-1 positive cells at precise periods of in vivodevelopment we have used a strategy based on cell specific toxicity. In the transgenic mouse studies presented here, Thy-1 positive cells are abiated by targeting the expression of the conditional toxin Herpes simplex virus 1 thymidine kinase (tk) with Thy-1 transcriptional control elements. We demonstrate the controlled expression of HSV1 tk in Thy-1 expressing cells of adult transgenic mice and the conditional abiation of >90% of maturing thymocytes. We describe the distinct subpopulations of cells remaining within individual ablated thymuses and show by phenotypic analyses that Thy-1 tk induced ablation enriches for CD4 low and double negative thymocytes. Furthermore, we demonstrate a differential effect of thymus directed ablation on the maturing peripheral T cell compartment at various times in mouse development. 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.

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