Figure 2.

 Engineering of brain‐selective ACE2 transgenic mouse models. (a) Syn‐hACE2 mice. The full open reading frame of the human ACE2 gene (hACE2) is driven by a synapsin promoter, and the syn‐hACE2 construct was injected into a 1‐cell mouse embryo. Transgenic syn‐hACE2 mice express hACE2 protein specifically in neurons. (b) ‘Brain‐only ACE2’ mice (bACE2). By breeding ACE2^−/y (white) with the syn‐hACE2 line (green), we generated a transgenic mouse model over‐expressing ACE2 in the brain while lacking the enzyme in the periphery (black). (c) SARA mice. The breeding strategy first consisted in generating double transgenic mice expressing both syn‐hACE2 (green) and R⁺ (human renin gene), or A⁺ (human AGT gene) constructs. These mice were then bred together to generate the triple transgenic SARA mice (yellow) in which brain‐selective over‐expression of ACE2 is in a position to counter the hyperactive RAS.