(A) Genomic PCR analysis of DNA isolated from brain (B), liver (L), and kidney (K) with primers amplifying the conditional (2-lox), the recombined (1-lox) and the WT allele. Recombination of the conditional allele was detected in brain, but not in liver or kidney, in GFAPCre+/HIF-1α^+f/+f, GFAPCre+/HIF-2α^+f/+f, and GFAPCre+/VHL^+f/+f mice, respectively (representative photograph). (B) Cre protein colocalizes with the astrocyte marker GFAP in the hippocampus of adult GFAPCre-positive animals (representative photographs). Scale bars: 100 μm. (C) Cre protein is expressed in brains of GFAPCre-positive animals, but not in liver and kidney (representative photographs). Scale bars: 100 μm. (D) Both HIF-1α and HIF-2α protein are not detectable in brain sections of GFAPCre–negative animals in normoxia. In contrast, both isoforms are strongly induced in brains of normoxic GFAPCre+/VHL^+f/+f mice (representative photographs). Scale bars: 100 μm. (E) HIF-α isoforms are not stabilized in livers and kidneys of GFAPCre+/VHL^+f/+f animals. WT animals treated with 0.1% carbon monoxide (CO) are shown as positive controls (representative photographs). Scale bars: 100 μm. (F) Immunoblots show the normoxic induction of both HIF-α isoforms in whole-brain lysates, but not in liver or kidney of GFAPCre+/VHL^+f/+f mice. The respective isoform is specifically deleted in brains of GFAPCre+/VHL^+f/+f/HIF-1α^+f/+f and GFAPCre+/VHL^+f/+f/HIF-2α^+f/+f double-knockout animals.