Thy-1 tk transgenic mice with a conditional lymphocyte deficiency.
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/lymphopoiesis 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 vivo development we have used a strategy based on cell specific toxicity. In the transgenic mouse studies presented here, Thy-1 positive cells are ablated 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 ablation 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.
Dzierzak
E
E
Laboratory of Gene Structure and Expression, National Institute for Medical Research, Mill Hill, London, UK.
Daly
B
B
Fraser
P
P
Larsson
L
L
Müller
A
A
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000502:physiology*; D018800:Thy-1 Antigens; D013937:Thymidine Kinase / Q000235:genetics*; D013950:Thymus Gland / Q000166:cytology
D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D013937:Thymidine Kinase