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Identification of a QTL on chromosome 1 for impaired autoregulation of RBF in fawn-hooded hypertensive rats

¹Kidney Disease Center, ³Human and Molecular Genetics Center, and Departments of ²Physiology, ⁷Medicine, ⁶Pediatrics, and ⁴Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin; and ⁵Department of Pediatric Surgery, Erasmus Medical Center, Rotterdam, The Netherlands

Submitted 19 August 2005 ; accepted in final form 16 November 2005

The present study evaluated whether the impairment in autoregulation of renal blood flow (RBF) in the fawn-hooded Hypertensive (FHH) rat colocalizes with the Rf-1 region on chromosome 1 that has been previously linked to the development of proteinuria in this strain. Autoregulation of RBF was measured in FHH and a consomic strain (FHH.1^BN) in which chromosome 1 from the Brown-Norway (BN) rat was introgressed into the FHH genetic background. The autoregulation indexes (AI) averaged 0.80 ± 0.08 in the FHH and 0.19 ± 0.05 in the FHH.1^BN rats. We next performed a genetic linkage analysis for autoregulation of RBF in 85 F2 rats generated from a backcross of FHH.1^BN consomic and FHH rats. The results revealed a significant quantitative trait locus (QTL) with a peak logarithm of the odds score of 6.3 near marker D1Rat376. To confirm the existence of this QTL, five overlapping congenic strains were created that spanned the region from markers D1Rat234 to D1Mit14. Transfer of a region of BN chromosome 1 from markers D1Mgh13 to D1Rat89 into the FHH genetic background improved autoregulation of RBF (AI = 0.23 ± 0.04) and reduced protein excretion. In contrast, RBF was poorly autoregulated and the rats were not protected from proteinuria in congenic strains in which other regions of chromosome 1 that exclude the D1Rat376 marker were transferred. These results indicate that there is a gene(s) that influences autoregulation of RBF and proteinuria between markers D1Mgh13 and D1Rat89 on chromosome 1 that lies within the confidence interval of the Rf-1 QTL previously linked to the development of proteinuria in FHH rats.

renal disease; Rf-1; consomic and congenic rats; quantitative trait locus

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