SD-Rosa-hAGT Rat

Catalog Number: CR004

Strain Name: SD-Gt(ROSA)26Sorem1(hAGT)/Cya

Genetic Background: Sprague-Dawley

Reproduction: Homozygote x Homozygote

 

Strain Description

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.

Strain Strategy


Figure 1. Gene editing strategy of SD-Rosa-hAGT rat. The “1.7 kb of 5'-flanking sequence-Human AGT DNA-1.3 kb of 3'-flanking sequence” cassette was cloned into intron 1 of ROSA26 in reverse orientation. The "Human AGT DNA" fragment contains the introns, exons, 5'UTR, and 3'UTR of the human AGT gene.

Application

  • Research on homeostatic regulation of blood pressure, body fluids, and electrolytes;
  • Research on primary hypertension and preeclampsia;
  • Research on renal tubular dysplasia.


Validation Data

1. Detection of human AGT protein


Figure 2. ELISA detection of human AGT protein expression in the serum of male and female 9-week-old SD-Rosa-hAGT rats (Rosa-hAGT) and wild-type rats (WT). The results indicate successful expression of human AGT protein in SD-Rosa-hAGT rat tissues, while wild-type rats do not exhibit human AGT protein expression.

 

 

References
[1]Lu H, Cassis LA, Kooi CW, Daugherty A. Structure and functions of angiotensinogen. Hypertens Res. 2016 Jul;39(7):492-500. doi: 10.1038/hr.2016.17. Epub 2016 Feb 18. Erratum in: Hypertens Res. 2016 Nov;39(11):827.
[2]Cusi D, Macciardi F, Barlassina C. Angiotensinogen gene polymorphism, again? J Hypertens. 2003 Oct;21(10):1815-8.
[3]Goldenberg I, Moss AJ, Ryan D, McNitt S, Eberly SW, Zareba W. Polymorphism in the angiotensinogen gene, hypertension, and ethnic differences in the risk of recurrent coronary events. Hypertension. 2006 Oct;48(4):693-9.
[4]Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol. 2004 Oct;287(4):F775-88.
[5]Hume GE, Fowler EV, Lincoln D, Eri R, Templeton D, Florin TH, Cavanaugh JA, Radford-Smith GL. Angiotensinogen and transforming growth factor beta1: novel genes in the pathogenesis of Crohn's disease. J Med Genet. 2006 Oct;43(10):e51.