Genetic background strongly influences the transition to chronic kidney disease of adriamycin nephropathy in mice

Watanabe, Masaki; Hiura, Koki; Sasaki, Hayato; Okamura, Tadashi; Sasaki, Nobuya

doi:10.1538/expanim.22-0057

Cited by 5 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The kidneys were used for PAS staining 7 days after ADR administration. According to established protocols [20], sections were treated with 0.5% periodic acid solution for 5 min, washed in distilled water, stained with Schiff's reagent (Fujifilm Wako Pure Chemical Corporation, Osaka, Japan) for 30 min, washed thrice with 0.8% sodium bisulfite solution for 3 min each, rinsed in running water, counterstained with hematoxylin for 4 min, washed in running water, rinsed in distilled water, cleared, and mounted. Kidneys were used for picrosirius red staining 28 days after ADR administration.…”

Section: Histologymentioning

confidence: 99%

“…Kidneys were used for picrosirius red staining 28 days after ADR administration. According to previous studies [20], sections were deparaffinized, washed in running water, rinsed in distilled water for 1 min, stained with solution A (0.5 g Sirius Red in 500 mL picric acid saturated solution) for 1 h, treated thrice with solution B (5 mL acetic acid in 1000 mL distilled water) for 3 s each, cleared, and mounted. Fibrosis was quantified using picrosirius red stained tissue sections.…”

Section: Histologymentioning

confidence: 99%

See 1 more Smart Citation

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy

Watanabe,

Ishii,

Hashimoto

et al. 2024

Genes

Self Cite

View full text Add to dashboard Cite

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the PrkdcR2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of ADR nephropathy in the FVB/N strain has yet to be conducted. Our research aimed to create a novel mouse model, the FVB-PrkdcR2140C, by introducing PrkdcR2140C into the FVB/NJcl (FVB) strain. Our study showed that FVB-PrkdcR2140C mice developed severe renal damage when exposed to ADR, as evidenced by significant albuminuria and tubular injury, exceeding the levels observed in C57BL/6J (B6)-PrkdcR2140C. This indicates that the FVB/N genetic background, in combination with the R2140C mutation, strongly predisposes mice to ADR nephropathy, highlighting the influence of genetic background on disease susceptibility. Using RNA sequencing and subsequent analysis, we identified several genes whose expression is altered in response to ADR nephropathy. In particular, Mmp7, Mmp10, and Mmp12 were highlighted for their differential expression between strains and their potential role in influencing the severity of kidney damage. Further genetic analysis should lead to identifying ADR nephropathy modifier gene(s), aiding in early diagnosis and providing novel approaches to kidney disease treatment and prevention.

show abstract

Section: Histologymentioning

confidence: 99%

Section: Histologymentioning

confidence: 99%

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy

Watanabe,

Ishii,

Hashimoto

et al. 2024

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the degree of renal injury in these models is heavily influenced by the strain, drug dosage and batches, and route of administration. 67 , 68 In particular, BALB/c mice are very sensitive to Adriamycin, but C57BL/6 strain is resistant. Some investigators use a high dose of Adriamycin protocol in mice with C57BL/6 background and show only limited success.…”

Section: Ckd Modelsmentioning

confidence: 99%

Animal Models of Kidney Disease: Challenges and Perspectives

Liang

Liu

2023

Kidney360

View full text Add to dashboard Cite

Kidney disease is highly prevalent and affects about 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies are incurable and often ineffective. Animal models are indispensable for understanding the pathophysiology of various kidney diseases and for preclinically testing novel remedies. In the last two decades, rodents continue to be the most used models for imitating human kidney diseases, largely due to the increasing availability of many unique genetically modified mice. Despite many limitations and pitfalls, animal models play an essential and irreplaceable role in gaining novel insights into the mechanisms, pathologies and therapeutic targets of kidney disease. In this review, we highlight commonly used animal models of kidney diseases by focusing on experimental acute kidney injury, chronic kidney disease, and diabetic kidney disease. We briefly summarize the pathological characteristics, advantages and drawbacks of some widely used models. Emerging animal models such as mini-pig, salamander, zebrafish and drosophila, as well as human-derived kidney organoids and kidney-on-a-chip are also discussed. Undoubtedly, careful selection and utilization of appropriate animal models is of vital importance in deciphering the mechanisms underlying nephropathies and evaluating the efficacy of new treatment options. Such studies will provide a solid foundation for future diagnosis, prevention and treatment of human kidney diseases.

show abstract

“…A standard laboratory diet, CE-2 (CLEA Japan), and tap water were available ad libitum. Data from BALB mice receiving ADR administration through the tail vein have also been published in a study conducted with the same protocol [6].…”

Section: Animalsmentioning

confidence: 99%

Differences in susceptibility to ADR nephropathy among C57BL/6 substrains

et al. 2023

Self Cite

View full text Add to dashboard Cite

Adriamycin (ADR) nephropathy is the most widely used nephropathy model to study the pathophysiological mechanisms of chronic kidney disease (CKD) in mice. However, its application is limited to a few mouse strains such as the BALB/c strain; the standard strain, C57BL/6J (B6J), does not develop ADR nephropathy. Nevertheless, Arif et al.reported that C57BL/6N (B6N), another standard strain, is ADR-susceptible. Since then, no follow-up reports or other studies have been published on ADR nephropathy in B6N mice.Therefore, the goal of this study was to determine whether B6N mice are indeed susceptible to ADR nephropathy and whether there are differences in ADR susceptibility among the substrains of C57BL/6NCrl (NCrl) and C57BL/6NJcl (NJcl). NCrl mice showed marked albuminuria and mesangial cell proliferation, which are associated with mild ADR nephropathy, confirming that NCrl mice were susceptible to ADR nephropathy.On the other hand, NJcl mice did not exhibit these symptoms. ADR nephropathy models are usually generated by administering ADR through the tail vein, but Arif et al.administered ADR through the orbital vein. Therefore, we investigated the effect of the route of administration on ADR nephropathy. The degree of ADR nephropathy was found to vary based on the route of administration: more severe nephropathy was observed upon administration through the tail vein than through the orbital vein. Therefore, we conclude that NCrl mice are susceptible to ADR nephropathy, and the severity of ADR-induced nephropathy through orbital vein administration is relatively lower than that through the tail vein.

show abstract

Genetic background strongly influences the transition to chronic kidney disease of adriamycin nephropathy in mice

Cited by 5 publications

References 30 publications

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy

Animal Models of Kidney Disease: Challenges and Perspectives

Differences in susceptibility to ADR nephropathy among C57BL/6 substrains

Contact Info

Product

Resources

About