(A) Generation of mice with inducible Kir6.2[K185Q,ΔN30] expression. The targeting strategy for generation of a Cre-inducible Kir6.2[K185Q,ΔN30] transgene in the ROSA26 locus is shown. ES cells were transfected with the depicted vector, and homologous recombinants were detected by Southern Blot (not shown). Correctly targeted ES cells were injected into blastocysts. (B) Cre-mediated recombination of the Neo/WSS cassette leads to expression of the Kir6.2[K185Q,ΔN30] protein but also to expression of a GFP via an internal ribosome entry site (IRES). Freshly isolated islets from Rip-Cre/Rosa26-Kir6.2[K185Q,ΔN30] (Rip-DTG) animals show diffuse green fluorescence in the core of the islet, reflecting transgene expression in β-cells. (C) Fed (solid) and fasted (dashed) blood glucose levels from Rip-DTG and control (WT, Rip-Cre and Rosa26-Kir6.2[K185Q,ΔN30] (Rosa-Kir6.2)) littermates over time (n=8–10 mice in each group, mean ± SEM). (D) Fed plasma insulin from all 4 genotype mice at 20–30 day-old and 50–100 day-old.