Early onset albuminuria in Dahl rats is a polygenetic trait that is independent from salt loading.
The aim of the study was to characterize the genetic basis for the early onset of increased urinary albumin excretion (UAE) observed in the salt-sensitive Dahl rat (SS). We first characterized blood pressures and UAE values in adult SS compared with the spontaneously hypertensive rat (SHR) strain. Blood pressure measurements by radiotelemetry at 14 wk demonstrated similar spontaneous hypertension in both strains on a low-sodium diet containing 0.2% NaCl by weight, whereas UAE was markedly increased in SS compared with SHR (253.07 +/- 68.39 vs. 1.65 +/- 1.09 mg/24 h, P < 0.0001). Analysis of UAE in young animals of both strains fed a low-sodium diet demonstrated that UAE is elevated in SS as early as 4 wk of age (P < 0.0001), when ultrastructural evaluation of glomeruli by electron microscopy appears still normal. At 8 wk SS demonstrated a 280-fold elevated UAE compared with SHR (P < 0.0001). Consequently, to identify quantitative trait loci (QTLs) contributing to salt-independent early manifestation of increased UAE in the SS rat, we performed genome-wide linkage and QTL mapping analysis in a young F(2) population derived from the two contrasting strains. UAE was determined in 539 F(2) animals at 8 wk. We identified seven suggestive or significant UAE QTLs on rat chromosomes (RNO) RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, and RNO19, accounting together for 34% of the overall variance of UAE in this F(2) population. Thus early onset albuminuria in the SS rat is under polygenetic influence and independent from salt loading.
Poyan Mehr
Ali
A
Institute of Clinical Pharmacology and Toxicology, Universitätsklinikum Benjamin Franklin Hospital, Freie Universität Berlin, Germany.
Siegel
Anja-Kristin
AK
Kossmehl
Peter
P
Schulz
Angela
A
Plehm
Ralph
R
de Bruijn
Jan A
JA
de Heer
Emile
E
Kreutz
Reinhold
R
D000419:Albuminuria / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D016678:Genome; D005838:Genotype; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D017673:Sodium Chloride, Dietary