Abrogation of IGF-1R signaling in thymocytes results in a decrease in thymic function and in peripheral T-cell and RTE populations that is restored by IGF-1 administration. (A) Schematic representation of IGF-1R/loxP mice illustrating the generation of T-IGF-1R⁻ mice upon cre-mediated deletion of exon 3 encoding the high-affinity binding site in cells expressing the proximal LCK promoter. Arrows indicate the location of PCR primers used in RT-PCR to confirm exon 3 deletion. (B) RT-PCR of sorted thymocyte and TEC populations confirming the loss of IGF-1R exon 3 expression in thymocytes in mice expressing the cre recombinase (−), but not in LSK, vascular endothelium (CD45⁻ CD31⁺), cTECs (CD45⁻ Ly51⁺ UEA-1⁻), or mTECs (CD45⁻ Ly51⁻ UEA-1⁺; +). (C) Decreased thymocyte populations in T-IGF-1R⁻ mice are associated with the loss of splenic naive CD4⁺ (D), CD8⁺ (E), and RTE (F) populations. n = 16 to 22 mice per experimental group combined from 4 independent experiments. *P < .05 between IGF-1– and diluent-treated mice. (G-I) T-IGF-1R⁻ mice and wild-type littermates lacking cre expression (T-IGF-1R⁺) were given a 2-week course of IGF-1 at a dose of 100 μg/day. (G) Thymocyte populations, (H) thymic TRECs (*P < .05 between each IGF-1 treatment group and both diluent control groups; #, P = .07 between diluent-treated T-IGF-1R⁺ and T-IGF-1R⁻ groups), and (I) peripheral LSK (*P < .05 between each IGF-1 treatment group and both diluent control groups) were enumerated. Shown are composite data of 2 independent experiments with 7 to 8 mice per experimental group. Error bars represent SEM.