A novel model of conditionally inducible angiotensin production in the brain: investigations of sodium and fluid intake

Transgenic mice expressing human renin via the neuron‐specific synapsin promoter (sR) were bred with ubiquitous CAG promoter, conditionally inducible human angiotensinogen (AGT) mice (A Red ). Recombination of the A Red transgene by Cre‐recombinase results in loss of a dsRed marker and gain of AGT expression. Adenovirus encoding Cre (AdCre) was injected into the lateral cerebral ventricle (ICV) of sRA Red and littermate control mice. At baseline, total fluid and sodium intakes of sRA Red mice (0.30±0.02 mL/day; 0.97±0.15 mEq/day, n=12) was similar to littermates (0.24±0.03 mL/day; 0.63±0.03 mEq/day, n=16) in a two‐bottle choice paradigm (water vs 0.15 M NaCl). Three weeks after AdCre injection, sRA Red mice increased both total fluid and sodium intakes in comparison to baseline (0.46±0.05 mL/day, P=0.01; 1.79±0.20 mEq/day, P<0.01, n=12) and littermate controls (0.27±0.04 mL/day, P<0.01; 1.03±0.11 mEq/day, P<0.01, n=16). Mice expressing a reporter construct sensitive to Cre‐recombination (ROSA‐tdTomato) were injected using the same methodology as the sRA Red mice. ICV delivery of AdCre into ROSA‐tdTomato mice resulted in reporter gene expression throughout the ependyma but also within the subfornical organ and median preoptic nucleus. We developed a model of conditionally inducible expression of AGT, which can be used to temporally and spatially control the production of angiotensin peptides in the brain.