The RenTg Mice

A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease

Anne Cecile Huby, Panagiotis Kavvadas, Carlo Alfieri, Ahmed Abed, Julie Toubas, Maria Pia Rastaldi, Jean Claude Dussaule, Christos Chatziantoniou, Christos E. Chadjichristos

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere52362
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 29 2012

Fingerprint

renin
kidney diseases
Chronic Renal Insufficiency
Renin
mice
Kidney
hypertension
cell adhesion
blood vessels
CD31 Antigens
Hypertension
animal models
kidneys
Renal Hypertension
Vascular Cell Adhesion Molecule-1
renin-angiotensin system
Sclerosis
Renin-Angiotensin System
Transgenes
sclerosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The RenTg Mice : A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease. / Huby, Anne Cecile; Kavvadas, Panagiotis; Alfieri, Carlo; Abed, Ahmed; Toubas, Julie; Rastaldi, Maria Pia; Dussaule, Jean Claude; Chatziantoniou, Christos; Chadjichristos, Christos E.

In: PLoS One, Vol. 7, No. 12, e52362, 29.12.2012.

Research output: Contribution to journalArticle

Huby, AC, Kavvadas, P, Alfieri, C, Abed, A, Toubas, J, Rastaldi, MP, Dussaule, JC, Chatziantoniou, C & Chadjichristos, CE 2012, 'The RenTg Mice: A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease', PLoS One, vol. 7, no. 12, e52362. https://doi.org/10.1371/journal.pone.0052362
Huby, Anne Cecile ; Kavvadas, Panagiotis ; Alfieri, Carlo ; Abed, Ahmed ; Toubas, Julie ; Rastaldi, Maria Pia ; Dussaule, Jean Claude ; Chatziantoniou, Christos ; Chadjichristos, Christos E. / The RenTg Mice : A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease. In: PLoS One. 2012 ; Vol. 7, No. 12.
@article{eb5648a31fdd4c4fada0b251090acb82,
title = "The RenTg Mice: A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease",
abstract = "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.",
author = "Huby, {Anne Cecile} and Panagiotis Kavvadas and Carlo Alfieri and Ahmed Abed and Julie Toubas and Rastaldi, {Maria Pia} and Dussaule, {Jean Claude} and Christos Chatziantoniou and Chadjichristos, {Christos E.}",
year = "2012",
month = "12",
day = "29",
doi = "10.1371/journal.pone.0052362",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - The RenTg Mice

T2 - A Powerful Tool to Study Renin-Dependent Chronic Kidney Disease

AU - Huby, Anne Cecile

AU - Kavvadas, Panagiotis

AU - Alfieri, Carlo

AU - Abed, Ahmed

AU - Toubas, Julie

AU - Rastaldi, Maria Pia

AU - Dussaule, Jean Claude

AU - Chatziantoniou, Christos

AU - Chadjichristos, Christos E.

PY - 2012/12/29

Y1 - 2012/12/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84871576753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871576753&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0052362

DO - 10.1371/journal.pone.0052362

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e52362

ER -