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Selective Expression of the Cre Recombinase in Late-Stage Thymocytes Using the Distal Promoter of the Lck Gene¹

Dong Ji Zhang^*, Qi Wang^*, Jie Wei^*, Gyulnar Baimukanova^*, Frank Buchholz, A. Francis Stewart, Xiaohong Mao and Nigel Killeen^2,*

^* Department of Microbiology and Immunology, University of California, San Francisco, California 94143; Max Planck Institute of Molecular Cell Biology and Genetics and Biotec, Technische Universität Dresden, Dresden, Germany; Functional Genomics Department, Novartis Pharmaceuticals Corporation, Summit, NJ 07901

Transgenic mouse lines were generated that express the Cre recombinase under the control of the distal promoter of the mouse Lck gene. Cre recombination in four of these lines of transgenic mice was characterized at the single cell level using ROSA26-regulated loxP-Stop-loxP-geo and loxP-Stop-loxP-YFP reporter mouse lines. Two of the lines showed T cell-restricted Cre recombination, whereas the other two also expressed Cre in B cells, NK cells, and monocytes. Cre recombination began at a late stage of T cell development (at or after up-regulation of the TCR during positive selection) in the two T cell-restricted lines. Lines of mice that express the Cre recombinase at late stages of thymocyte development are of value for determining the impact of mutations on T cell function in the absence of complicating effects on early thymocyte selection.

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