A single amino acid substitution in PRKDC is a determinant of sensitivity to Adriamycin-induced renal injury in mouse.

Masaki Watanabe, Yuki Takahashi, Koki Hiura, Kenta Nakano, Tadashi Okamura, Hayato Sasaki, Nobuya Sasaki

Biochemical and biophysical research communications 2021 Jun 04

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Adriamycin (ADR)-induced nephropathy is frequently utilized in rodent models of podocytopathy. However, the application of this model in mice is limited to a few strains, such as BALB/c mice. The most commonly used mouse strain, C57BL/6 (B6), is resistant to ADR-induced nephropathy, as are all mouse strains with a B6 genetic background. Reportedly, the R2140C variant of the Prkdc gene is the cause of susceptibility to ADR-induced nephropathy in mice. To verify this hypothesis, we produced Prkdc mutant B6 mice, termed B6-PrkdcR2140C, that possess the R2140C mutation. After administration of ADR, B6-PrkdcR2140C mice exhibited massive proteinuria and glomerular and renal tubular injuries. In addition, there was no significant difference in the severity between B6-PrkdcR2140C and BALB/c. These findings demonstrated that B6-PrkdcR2140C show ADR-induced nephropathy susceptibility at a similar level to BALB/c, and that the PRKDC R2140C variant causes susceptibility to ADR-induced nephropathy. In future studies, ADR-induced nephropathy may become applicable to various kinds of genetically modified mice with a B6 background by mating with B6-PrkdcR2140C. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Masaki Watanabe, Yuki Takahashi, Koki Hiura, Kenta Nakano, Tadashi Okamura, Hayato Sasaki, Nobuya Sasaki. A single amino acid substitution in PRKDC is a determinant of sensitivity to Adriamycin-induced renal injury in mouse. Biochemical and biophysical research communications. 2021 Jun 04;556:121-126