Abstract
Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning approximately 8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD.