Genetic linkage of urinary albumin excretion in Dahl salt-sensitive rats: influence of dietary salt and confirmation using congenic strains

Physiol Genomics. 2006 Mar 13;25(1):39-49. doi: 10.1152/physiolgenomics.00150.2005.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Albuminuria / genetics*
  • Albuminuria / physiopathology
  • Animals
  • Animals, Congenic
  • Blood Pressure / genetics
  • Chromosome Mapping
  • Crosses, Genetic
  • Genetic Linkage*
  • Proteinuria / genetics*
  • Proteinuria / physiopathology
  • Quantitative Trait Loci
  • Rats
  • Rats, Inbred Dahl
  • Rats, Inbred SHR
  • Sodium Chloride, Dietary / administration & dosage*

Substances

  • Sodium Chloride, Dietary