Abstract
The fawn hooded hypertensive (FHH) rat is a well established model for hypertension and chronic kidney disease. We have performed an F2 linkage analysis between the FHH and the renal resistant and normotensive August Copenhagen Irish (ACI) strain to find quantitative trait loci (QTL) that show linkage to measures of renal impairment. Five renal failure QTL were mapped in this cross (Rf‐1 through Rf‐5), and these QTL interact with one another to produce a synergistic increase in renal impairment. To investigate the individual contribution of the Rf‐3 QTL, which is located on chromosome three, to the progression of kidney disease we have developed congenic animals that have an ACI background, and are FHH on Rf‐3, as well as Rf‐1 (rat chromosome 1) and Rf‐4 (rat chromosome 14). This triple congenic model allows us to investigate the interaction between genes in the Rf‐3 region with genes in these other two renal failure QTL. Based on proteinuria and microalbuminuria levels (figure 1) of the triple congenic animals, we have determined that genes in Rf‐3 significantly contribute to the onset and progression of kidney disease in the FHH rat. We have subsequently generated subcongenic animals targeting the Rf‐3 region to narrow the list of candidate genes, so that we can determine which specific gene(s) is contributing to observed renal impairment phenotype.
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