The T lymphocyte-specific protein tyrosine kinase p56 l c k (Lck) is an essential component of the TCR-mediated signal transduction complex. Lck knockout mice have reduced numbers of double-positive thymocytes and very few mature single-positive cells, particularly of the CD4 lineage. Here we demonstrate the ability of a tetracycline-based tissue-specific inducible Lck transgene to restore expansion of early thymocytes and maturation of single-positive cells in Lck n e g mice upon induction with doxycycline. Restoration of Lck expression is particularly important for positive selection to the CD4 + lineage but has a lesser impact on selection to the CD8 + lineage, suggesting activation of Lck is an important component of the signals involved in lineage choice during thymic differentiation.
