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Updated: May 15, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
The RenTg mice: a powerful tool to study renin-dependent chronic kidney disease
Anne-Cecile Huby1, Panagiotis Kavvadas, Carlo Alfieri
1Institut National de la Santé et de la Recherche Médicale Joint Research Unit S 702, Batiment Recherche, Tenon Hospital, Paris, France.
Background:
Several studies have shown that activation of the renin-angiotensin system may lead to hypertension, a major risk factor for the development of chronic kidney disease (CKD). The existing hypertension-induced CDK mouse models are quite fast and consequently away from the human pathology. Thus, there is an urgent need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. The objective of this study was dual: to investigate whether mice overexpressing renin could mimic the kinetics and the physiopathological characteristics of hypertension-induced renal disease and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD.
Methodology/Principal Findings:
We used a novel transgenic strain, the RenTg mice harboring a genetically clamped renin transgene. At 3 months, heterozygous mice are hypertensive and slightly albuminuric. The expression of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are increased in the renal vasculature indicating initiation of endothelial dysfunction. At 5 months, perivascular and periglomerular infiltrations of macrophages are observed. These early renal vascular events are followed at 8 months by leukocyte invasion, decreased expression of nephrin, increased expression of KIM-1, a typical protein of tubular cell stress, and of several pro-fibrotic agents of the TGFβ family. At 12 months, mice display characteristic structural alterations of hypertensive renal disease such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion and tubular dilation.
Conclusions/Significance:
The RenTg strain develops CKD progressively. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide new insights into the mechanisms of chronic renal failure and help to identify new targets for arresting and/or reversing the development of the disease.
Insights
A novel mouse model (RenTg) progressively develops chronic kidney disease (CKD) mimicking human pathology. This model reveals early endothelial dysfunction preceding structural damage, offering insights into CKD progression.
Area of Science:
- Nephrology
- Cardiovascular Research
- Translational Medicine
Background:
- Renin-angiotensin system activation is linked to hypertension and chronic kidney disease (CKD).
- Existing hypertension-induced CKD mouse models do not accurately reflect human disease progression.
- A need exists for a mouse model to study the pathogenesis of progressive renal disease.
Purpose of the Study:
- To investigate if renin-overexpressing mice (RenTg) replicate the kinetics and pathology of hypertension-induced renal disease.
- To identify cellular and molecular events in CKD progression using the RenTg model.
Main Methods:
- Utilized a novel transgenic RenTg mouse strain with a clamped renin transgene.
- Monitored hypertensive and albuminuric status, renal vascular markers, immune cell infiltration, and gene expression over 12 months.
- Assessed structural renal alterations characteristic of hypertensive renal disease.
Main Results:
- RenTg mice exhibited progressive hypertension and albuminuria starting at 3 months.
- Early signs included increased adhesion molecules (VCAM-1, PECAM-1) indicating endothelial dysfunction.
- Later stages (8-12 months) showed macrophage infiltration, nephrin downregulation, KIM-1 upregulation, pro-fibrotic factor increase, and structural damage (glomerular ischemia, sclerosis, mesangial expansion, tubular dilation).
Conclusions:
- The RenTg mouse strain provides a progressive model for studying hypertension-induced CKD.
- Endothelial dysfunction is an early pathogenic event preceding structural and fibrotic changes in this model.
- This model offers new insights into CKD mechanisms and potential therapeutic targets for renal failure.
