Genetic linkage of urinary albumin excretion in Dahl salt-sensitive rats: influence of dietary salt and confirmation using congenic strains.
Previously, we reported a linkage analysis for urinary albumin excretion (UAE) from a backcross population derived from the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR) raised on a low-salt diet. The present study sought to examine the effect of salt loading on the observation of UAE quantitative trait loci (QTL) using a F1(S x SHR) x S backcross population (n = 228) raised on a 2% NaCl diet. Parental strain data demonstrated that S rats have significantly higher blood pressure (BP) and UAE compared with either F1(S x SHR) or SHR at 8 wk of age, and this difference was exacerbated by 12 wk of age in response to a high-salt diet (2% NaCl). Genome scans done at 8, 12, and 16 wk of age yielded eight QTL for UAE. At week 8 (low salt), QTL for UAE were observed on rat chromosomes (RNO) 1, 2, 6, 8, 9, 11, 13, and 19. Week 8 linkage analysis confirmed previous linkage data and provided a baseline to examine the effect of salt loading at subsequent time points. At weeks 12 and 16 (after salt- loading), QTL for UAE were observed on RNO1, -6, -8, -9, and -13. Surprisingly, UAE QTL were no longer observed on RNO2, -11, and -19 after salt loading, suggesting that these QTL are attenuated by increased salt intake. The effects of UAE QTL on RNO2, -6, -9, -11, and -13 were examined using congenic strains whereby the SHR alleles at each QTL were placed on the S background. These congenic strains demonstrated large and significant effects on UAE compared with the S rat, proving that QTL for UAE reside on these chromosomes.
Department of Physiology and Cardiovascular Genomics, Medical University of Ohio, Toledo, Ohio 43614-5804, USA. mgarrett@meduohio.edu
Michael R
MR
Garrett
Bina
B
Joe
Shane
S
Yerga-Woolwine
D000367:Age Factors; D000419:Albuminuria / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D008040:Genetic Linkage; D011507:Proteinuria / Q000235:genetics* / Q000503:physiopathology; D040641:Quantitative Trait Loci; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D017673:Sodium Chloride, Dietary