Targeting SUR1/Abcc8-type neuroendocrine KATP channels in pancreatic islet cells

ATP-sensitive K+ (KATP) channels play a regulatory role in hormone-secreting pancreatic islet α-, β- and δ-cells. Targeted channel deletion would assist analysis and dissection of the intraislet regulatory network. Toward this end Abcc8/Sur1 flox mice were generated and tested by crossing with glucagon-(GCG)-cre mice to target α-cell KATP channels selectively. Agonist resistance was used to quantify the percent of α-cells lacking channels. 41% of Sur1(loxP/loxP);GCG-cre+ and ∼64% of Sur1(loxP/-);GCG-cre+ α-cells lacked KATP channels, while ∼65% of α-cells expressed enhanced yellow fluorescent protein (EYFP) in ROSA-EYFP/GCG-cre matings. The results are consistent with a stochastic two-recombination event mechanism and a requirement that both floxed alleles are deleted.