Time-Course Genetic Analysis of Albuminuria in Dahl Salt-Sensitive Rats on Low-Salt Diet

Abstract

ABSTRACT. The Dahl salt-sensitive hypertensive (S) rat develops albuminuria early in life even on a low-salt diet. In contrast, the spontaneously hypertensive rat (SHR) is highly resistant to developing albuminuria despite elevated BP. AnF1hybrid of S and SHR showed a low urinary albumin excretion (UAE) and low urinary protein excretion (UPE) similar to SHR,i.e., SHR was dominant. A genetic analysis was carried out on a large population (n= 276) obtained by backcrossingF1rats to the recessive S strain; the population was fed a low-salt diet. Genome scans done at 8, 12, and 16 wk of age yielded ten quantitative trait loci (QTL) for UAE and/or UPE with variable time-course patterns on nine rat chromosomes (RNO),i.e., RNO1, RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, RNO13, and RNO19. There were two UPE QTL on RNO6. At most of the UAE and/or UPE QTL, the S allele was associated with increased excretion, except for one of the QTL on RNO6 and the QTL on RNO11, where the S allele caused decreased excretion. Only the UAE and UPE QTL on RNO10 co-localized with a BP QTL. The S allele on RNO10 caused higher BP and higher UAE. Two additional BP QTL were detected on RNO1 and RNO6. Most of the UAE and UPE QTL co-localized with QTL for kidney lesions characteristic of S rats. Multiple interactions were observed for UAE, many of which involved RNO2. In summary, UAE is highly polygenic and the majority of the QTL altering UAE do not co-localize with QTL for BP as evaluated by tail-cuff measurements of BP. E-mail: mgarrett@mco.edu