Angiotensinogen (mutated mouse L11V;Y12I) (AGT (L11V;Y12I))

Angiotensinogen (AGT) is a member of the serpin family (Serpin A8) and serves as the essential precursor for all angiotensin peptides within the renin-angiotensin system (RAS) [UniProt P11859]. The mutated mouse L11V;Y12I variant is a specific transgenic product where the mouse protein has been modified at the leucine-11 and tyrosine-12 positions to valine and isoleucine, respectively [PubMed 7513297]. This modification humanizes the renin cleavage site, overcoming the high species specificity of renin and allowing human renin to efficiently cleave the mouse substrate into Angiotensin I [PubMed 8500303]. This mutated protein is a cornerstone of the Tsukuba hypertensive mouse model, which is used extensively in pharmacology to evaluate human-specific RAS inhibitors like the renin inhibitor aliskiren [PubMed 24107131]. While traditionally viewed as a substrate, AGT has recently emerged as a direct therapeutic target for RNA interference (RNAi) therapies, such as Zilebesiran, which aim to lower blood pressure by reducing hepatic AGT production [NEJM 2023; 389:325-335]. In transgenic models, the expression of this mutated product leads to chronic hypertension and associated cardiovascular damage, providing a robust platform for studying antihypertensive drug efficacy and safety.

Other names

Humanized mouse angiotensinogenmAGT-L11V/Y12ISerpin A8 (mutated)Alpha-2-globulinPre-angiotensinogen

Substrate for renin cleavage; target for RNA interference or antisense oligonucleotides to reduce systemic angiotensinogen levels and downstream Angiotensin II production