SD-Rosa-hAGT Rat

The AGT gene encodes the precursor of angiotensinogen, primarily expressed in the liver. It serves as a rate-limiting substrate in the renin-angiotensin system (RAS). When blood pressure decreases, the angiotensinogen precursor is cleaved by renin to generate angiotensin I (Ang I) in response. Subsequently, Ang I is further processed by angiotensin-converting enzyme (ACE) to produce the physiologically active enzyme angiotensin II (Ang II), which regulates blood pressure ^[1]. This protein is involved in maintaining blood pressure, body fluid, and electrolyte homeostasis, and plays a role in the pathogenesis of primary hypertension and preeclampsia ^[2-3]. Mutations in the AGT gene are closely associated with susceptibility to primary hypertension and can lead to renal tubular dysplasia ^[4]. Additionally, defects in this gene are associated with non-familial structural atrial fibrillation and inflammatory bowel disease ^[5].

The SD-Rosa-hAGT rat is a humanized model created by integrating the human AGT gene into the ROSA26 safe harbor locus in rats. The humanized region includes AGT gene introns, exons, 5’ UTR, and 3’ UTR, making it suitable for most drug screening studies targeting AGT. This model can be used for investigating the pathogenic mechanisms and drug development related to primary hypertension, pre-eclampsia, renal tubular dysplasia, non-familial structural atrial fibrillation, and inflammatory bowel disease.