The REN gene encodes renin, a crucial aspartyl protease and the rate-limiting enzyme of the renin-angiotensin system (RAS), which is fundamental for regulating blood pressure and electrolyte balance ^[1]. Primarily expressed in the juxtaglomerular cells of the kidneys, renin is secreted into the bloodstream where it functions to cleave angiotensinogen, produced by the liver, into angiotensin I ^[2]. This initiates a cascade leading to the formation of angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release from the adrenal glands, ultimately increasing blood pressure and sodium retention ^[3]. Mutations in the REN gene have been linked to several renal disorders, including familial juvenile hyperuricemic nephropathy type II, familial hyperreninemia, and renal tubular dysgenesis ^[4]. SD-H11-hREN rats are a humanized model generated using gene editing technology, in which the “3 kb of 5’- flanking sequence-Human REN DNA-1.2 kb of 3'-flanking sequence” cassette was inserted into H11 locus. Homozygous SD-H11-hREN rats are viable and fertile. This model can be used for research on the regulation of blood pressure, body fluid, and electrolyte homeostasis, as well as for studying the pathogenic mechanisms and drug development for various hereditary kidney diseases such as renal tubular dysgenesis and familial hyperreninemia.

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 REN gene encodes renin, another integral component of the RAS, which is fundamental for regulating blood pressure and electrolyte balance ^[6]. Primarily expressed in the juxtaglomerular cells of the kidneys, renin is secreted into the bloodstream where it functions to cleave angiotensinogen, produced by the liver, into angiotensin I ^[7]. This initiates a cascade leading to the formation of angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release from the adrenal glands, ultimately increasing blood pressure and sodium retention ^[8]. Mutations in the REN gene have been linked to several renal disorders, including familial juvenile hyperuricemic nephropathy type II, familial hyperreninemia, and renal tubular dysgenesis ^[9]. The SD-Rosa-hAGT/H11-hREN rats are a humanized model obtained by mating SD-Rosa-hAGT rats with SD-H11-hREN rats. This model can be used for research on the regulation of blood pressure, body fluid and electrolyte homeostasis, and the pathological mechanisms and treatment methods of primary hypertension, preeclampsia, renal tubular hypoplasia, non-familial structural atrial fibrillation, inflammatory bowel disease, etc. Moreover, it can be applied to the development of antihypertensive drugs targeting the renin-angiotensin system (RAS).

Abhd17a is located on chromosome 10 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Abhd17a conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.

R3hdm1 is located on chromosome 1 of mice. Nuclease Technology will be used to design sgRNA; R3hdm1 knockout mice will be obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.