Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice

Abstract A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line ha...

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Main Authors: Cyril Mousseaux, Tiffany Migeon, Perrine Frère, Marie Christine Verpont, Elisabeth Lutete, Claire Navarro, Liliane Louedec, Juliette Hadchouel
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.15443
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author Cyril Mousseaux
Tiffany Migeon
Perrine Frère
Marie Christine Verpont
Elisabeth Lutete
Claire Navarro
Liliane Louedec
Juliette Hadchouel
author_facet Cyril Mousseaux
Tiffany Migeon
Perrine Frère
Marie Christine Verpont
Elisabeth Lutete
Claire Navarro
Liliane Louedec
Juliette Hadchouel
author_sort Cyril Mousseaux
collection DOAJ
description Abstract A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3‐ and 6‐month‐old NPHS2‐Cre+/− mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2‐Cre+/− mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune‐mediated severe glomerular insult, the anti‐glomerular basement membrane glomerulonephritis model (anti‐GBM‐GN) in 3‐month‐old control and NPHS2‐Cre+/− mice. NPHS2‐Cre+/− mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2‐Cre+/− transgenic mice on a C57BL/6J background can be safely used for podocyte‐specific gene inactivation in control conditions and in the anti‐GBM‐GN model.
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spelling doaj.art-969940e1b3094259a0985b2e387fec672023-12-11T09:36:42ZengWileyPhysiological Reports2051-817X2022-09-011017n/an/a10.14814/phy2.15443Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J miceCyril Mousseaux0Tiffany Migeon1Perrine Frère2Marie Christine Verpont3Elisabeth Lutete4Claire Navarro5Liliane Louedec6Juliette Hadchouel7Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique 1155, Tenon Hospital Paris FranceAbstract A recent article described a thickening of the glomerular basement membrane (GBM) along with changes in the expression of key components of the extracellular matrix in 6‐month‐old NPHS2‐Cre transgenic mice, which express the Cre recombinase specifically in podocytes. This transgenic line has been widely used to characterize the implication of candidate genes in glomerular diseases in younger mice. Using a different mouse strain (C57BL/6J) than the previous report (129S6/SvEvTac), we sought to characterize 3‐ and 6‐month‐old NPHS2‐Cre+/− mice in control and pathological conditions. At baseline, there was no difference in renal function and histology between control and NPHS2‐Cre+/− mice. Notably, GBM thickness evaluated by transmission electron microscopy was similar between the two groups. We then induced an immune‐mediated severe glomerular insult, the anti‐glomerular basement membrane glomerulonephritis model (anti‐GBM‐GN) in 3‐month‐old control and NPHS2‐Cre+/− mice. NPHS2‐Cre+/− mice exhibited the same alterations in renal function and structure as control mice. In summary, our study strongly suggests that NPHS2‐Cre+/− transgenic mice on a C57BL/6J background can be safely used for podocyte‐specific gene inactivation in control conditions and in the anti‐GBM‐GN model.https://doi.org/10.14814/phy2.15443crescentic glomerulonephritismouse modelsNPHS2‐CreNTS
spellingShingle Cyril Mousseaux
Tiffany Migeon
Perrine Frère
Marie Christine Verpont
Elisabeth Lutete
Claire Navarro
Liliane Louedec
Juliette Hadchouel
Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
Physiological Reports
crescentic glomerulonephritis
mouse models
NPHS2‐Cre
NTS
title Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
title_full Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
title_fullStr Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
title_full_unstemmed Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
title_short Heterozygous expression of Cre recombinase in podocytes has no impact on the anti‐glomerular basement membrane glomerulonephritis model in C57BL/6J mice
title_sort heterozygous expression of cre recombinase in podocytes has no impact on the anti glomerular basement membrane glomerulonephritis model in c57bl 6j mice
topic crescentic glomerulonephritis
mouse models
NPHS2‐Cre
NTS
url https://doi.org/10.14814/phy2.15443
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