Unraveling the genetics of chronic kidney disease using animal models

Abstract

Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to human disease. Therefore, we reviewed the literature on genetic studies of kidney disease in rat and mouse and examined the concordance between kidney disease QTL across species. Fifteen genomic regions contribute to kidney disease in the rat, with 12 replicated either in a separate rat cross or in another species. Five loci found in humans were concordant to QTL found in the rat. Two of these were found by homology to a previously identified rat QTL on chromosome 1, demonstrating that kidney disease loci in animal models can predict the location of kidney disease loci in humans. In contrast to the rat, the mouse has been underutilized in the genetic analysis of polygenic kidney disease, although mutagenesis and QTL analysis in the mouse are likely to contribute new findings in the near future. Knowledge of kidney disease loci conserved between the mouse and rat will identify prime candidate loci to test for association with chronic kidney disease in humans.