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

Animal models of podocytopathy and chronic kidney diseases (CKD) help elucidate these pathologies. Adriamycin (ADR)-induced nephropathy is a common rodent model of podocytopathy. BALB/c mice are sensitive to ADR, whereas C57BL/6 (B6) mice, the most commonly used strain, are resistant to ADR. Therefore, mouse strains with the B6 genetic background cannot be used as an ADR nephropathy model. We previously generated DNA-dependent protein kinase catalytic subunit (Prkdc) mutant B6 mice (B6-Prkdc(R2140C)) carrying the R2140C mutation that causes ADR nephropathy. However, whether ADR nephropathy in the novel strain progresses to CKD after ADR administration has not been evaluated. Therefore, we examined whether the B6-PrkdcR2140C mice develop CKD after ADR administration. We also evaluated whether differences existed in the genetic background in ADR nephropathy by comparing the B6-Prkdc(R2140C) mice with BALB/c mice. Our findings demonstrated that B6-Prkdc(R2140C) progresses to CKD and is resistant to nephropathy compared with the BALB/c mice. The B6Prkdc(R2140C) and BALB/c mice differed in the expression of genes related to inflammatory mediators, and further analysis is required to identify factors that contribute to resistance to nephropathy.

Automated summary

Animal models are useful for studying podocytopathy and chronic kidney diseases. ADR-induced nephropathy in rodents is a common model for podocytopathy. A new strain of mutant B6 mice with ADR nephropathy was developed and found to progress to CKD. Comparisons with BALB/c mice revealed genetic background differences related to inflammatory mediators and further analysis is needed.