1. ¹Department of Medicine, Duke University, Durham, North Carolina, USA
2. ²Department of Medicine, Durham VA Medical Center, Durham, North Carolina, USA
3. ³Department of Pathology, University of Miami, Miami, Florida, USA
4. ⁴Department of Genetics, Duke University Medical Center, Durham, North Carolina, USA

Correspondence: TH Le, Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, MSRB II, 106 Research Drive, Room 2018, Durham, North Carolina 27710, USA. E-mail: thu.le@duke.edu

Received 28 November 2006; Revised 29 June 2007; Accepted 3 July 2007; Published online 12 September 2007.

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 8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD.