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International Immunology, Vol. 5, No. 8, pp. 975-984,August 1993
© 1993 Japanese Society for Immunology

Thy-1 tk transgenic mice with a conditional lymphocyte deficiency

Elaine Dzierzak, Bernadette Daly, Peter Fraser, Lena Larsson and Albrecht Müller

Laboratory of Gene Structure and Expression, National Institute for Medical Research The Ridgeway, Mill Hill, London NW7 1AA, UK

Correspondence to: Correspondence to: E. Dzierzak

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.

Keywords: ablation, conditional ablation, ganciclovir, hematopotetic development, in vivo enrichment, Thy-1 gene expression, Thy-1 positive lymphocytes

Received 28 January 1993, accepted 12 May 1993.


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