Genetic loci that affect aristolochic acid induced nephrotoxicity in the mouse.

Am J Physiol Renal Physiol. 2011 Mar 23;

Authors: Rosenquist TA

Aristolochic acids (AA) are plant-derived nephrotoxins and carcinogens found in traditional medicines and herbal remedies. AA causes aristolochic acid nephropathy (AAN) and is a suspected environmental agent in Balkan endemic nephropathy (BEN) and its associated upper urothelial cancer. Approximately 5-10% of individuals exposed to AA develop renal insufficiency and/or cancer; thus a genetic predisposition to AA-sensitivity has been proposed. The mouse is an established animal model of AAN and inbred murine strains vary in AA sensitivity confirming the genetic predisposition. We mapped quantitative trait loci (QTL) correlated with proximal tubule dysfunction after exposure to AA in an F2 population of mice, derived from breeding an AA-resistant strain (C57BL/6J) and an AA-sensitive strain (DBA/2J). A single main QTL was identified on Chromosome 4 (Aanq1); 3 other interacting QTLs, (Aanq2-4), also were detected. The Aanq1 region was also detected in untreated mice, raising the possibility that pre-existing differences in proximal tubule function may affect the severity of AA-elicited toxicity. This study lays the groundwork for identifying the genetic pathways contributing to aristolochic acid sensitivity in the mouse and will further our understanding of human susceptibility to aristolochic acid found widely in traditional medicines.

PMID: 21429970 [PubMed - as supplied by publisher]

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