Interstrain Differences in Murine Daunomycin-Induced Nephrosis

Abstract

Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.