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Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6

Adriamycin (ADR)-induced nephropathy remains the leading model to study human primary focal segmental glomerulosclerosis (FSGS), a common pathway for podocyte damage and glomerular loss of function that leads to chronic kidney disease. However, the use of this model for reverse genetics is limited b...

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Autores principales: Bryant, Claire, Cianciolo, Rachel, Govindarajan, Rajgopal, Agrawal, Shipra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243439/
https://www.ncbi.nlm.nih.gov/pubmed/35784478
http://dx.doi.org/10.3389/fcell.2022.924751
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author Bryant, Claire
Cianciolo, Rachel
Govindarajan, Rajgopal
Agrawal, Shipra
author_facet Bryant, Claire
Cianciolo, Rachel
Govindarajan, Rajgopal
Agrawal, Shipra
author_sort Bryant, Claire
collection PubMed
description Adriamycin (ADR)-induced nephropathy remains the leading model to study human primary focal segmental glomerulosclerosis (FSGS), a common pathway for podocyte damage and glomerular loss of function that leads to chronic kidney disease. However, the use of this model for reverse genetics is limited by historical categorization of C57BL/6 mice as an ADR-resistant strain, which is also the most common genetically modified strain. Additionally, conflicting reports exist utilizing C57BL/6 for ADR-nephrosis due to lack of understanding of substrain differences (J/N) and variability in ADR dosage, timing, and frequency to induce damage. We have undertaken a systematic approach to elucidate the specifics of ADR-nephrosis in C57BL/6 N and J substrains. We induced nephropathy with 2 doses of ADR, and measured albuminuria for 6 weeks and performed histological evaluations. Our findings revealed induction of robust and modest proteinuria in N and J substrains, respectively. The serum creatinine levels were elevated in N, but not J substrain. Both the substrains showed reduction in body weight with N greater than J, although mortality remained at 0% in both substrains. Histological analysis showed worse renal lesions in the N than the J substrain. Podocyte markers synaptopodin, nephrin, podocin, and WT1 were reduced to a greater extent in the N than the J substrain. In summary, we provide the nephrology community with a reproducible mouse model for FSGS, in a strain otherwise assumed to be ADR-resistant and highlight the differences between J and N substrains. This enables future studies, especially concerning genetically manipulated animal models in C57BL/6.
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spelling pubmed-92434392022-07-01 Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6 Bryant, Claire Cianciolo, Rachel Govindarajan, Rajgopal Agrawal, Shipra Front Cell Dev Biol Cell and Developmental Biology Adriamycin (ADR)-induced nephropathy remains the leading model to study human primary focal segmental glomerulosclerosis (FSGS), a common pathway for podocyte damage and glomerular loss of function that leads to chronic kidney disease. However, the use of this model for reverse genetics is limited by historical categorization of C57BL/6 mice as an ADR-resistant strain, which is also the most common genetically modified strain. Additionally, conflicting reports exist utilizing C57BL/6 for ADR-nephrosis due to lack of understanding of substrain differences (J/N) and variability in ADR dosage, timing, and frequency to induce damage. We have undertaken a systematic approach to elucidate the specifics of ADR-nephrosis in C57BL/6 N and J substrains. We induced nephropathy with 2 doses of ADR, and measured albuminuria for 6 weeks and performed histological evaluations. Our findings revealed induction of robust and modest proteinuria in N and J substrains, respectively. The serum creatinine levels were elevated in N, but not J substrain. Both the substrains showed reduction in body weight with N greater than J, although mortality remained at 0% in both substrains. Histological analysis showed worse renal lesions in the N than the J substrain. Podocyte markers synaptopodin, nephrin, podocin, and WT1 were reduced to a greater extent in the N than the J substrain. In summary, we provide the nephrology community with a reproducible mouse model for FSGS, in a strain otherwise assumed to be ADR-resistant and highlight the differences between J and N substrains. This enables future studies, especially concerning genetically manipulated animal models in C57BL/6. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243439/ /pubmed/35784478 http://dx.doi.org/10.3389/fcell.2022.924751 Text en Copyright © 2022 Bryant, Cianciolo, Govindarajan and Agrawal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bryant, Claire
Cianciolo, Rachel
Govindarajan, Rajgopal
Agrawal, Shipra
Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title_full Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title_fullStr Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title_full_unstemmed Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title_short Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6
title_sort adriamycin-induced nephropathy is robust in n and modest in j substrain of c57bl/6
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243439/
https://www.ncbi.nlm.nih.gov/pubmed/35784478
http://dx.doi.org/10.3389/fcell.2022.924751
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