(A) Cre recombinase was inserted into the Gcg gene locus of BAC RP23-242F22 at the ATG start codon. Red boxes, 5′ and 3′ untranslated regions; white boxes, Gcg exons; lines, intronic DNA. (B–I) Cre recombinase expression within GCG neurons was visualized by crossing Gcg-Cre mice with tdTomato reporter animals. tdTomato fluorescence (NTS in C; VLM in F) is restricted to GLP-1–expressing cells (B and E) in the NTS (D) and the VLM (G). Specificity of Cre recombinase expression is high, with virtually all tdTomato-labeled cells in the NTS (99%) and more than 92% in the VLM showing GLP-1 immunofluorescence (H). The majority of GLP-1–labeled neurons show Cre recombinase activity, with efficacy ranging from 84% in the VLM to 93% in the NTS (I). The few GLP-1–positive neurons that lack tdTomato signal are marked with green asterisks (in B, D, E, and G). (J and K) PVH and arcuate nuclei (Arc) neurons did not show expression, but tdTomato-labeled axons and terminals originating from brainstem GCG neurons were readily observed. AHE, anterior hypothalamic nucleus; ME, median eminence. (L–O) GCG-Gq DREADD transgenic mice exhibit normal body weight (L), daily chow food intake (M), and normal fed (N) and fasting (O) glucose levels. Scale bars in B–G, J, and K are in micrometers.