Faculty Collaboration Database

Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol 2008 Sep;295(3):F837-42

Date

07/26/2008

Pubmed ID

18653478

Pubmed Central ID

PMC2536867

DOI

10.1152/ajprenal.90341.2008

Scopus ID

2-s2.0-54449084434 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the 20 autosomes and the X and Y chromosomes were individually transferred from the Brown Norway (BN) rat onto the Dahl SS/Mcwi genetic background. Male and female rats of each of the two parental and 22 consomic strains (10-12 rats/group) were fed a high-salt (8.0% NaCl) diet for 3 wk. Mean arterial blood pressure rose by 60 mmHg and urinary protein and albumin excretion increased 3- and 20-fold, respectively, in male SS/Mcwi rats compared with BN controls. Substitution of chromosomes 1, 5, 7, 8, 13, or 18 from the BN onto the SS/Mcwi background attenuated the development of hypertension, proteinuria, and albuminuria in male rats. In female rats, substitution of chromosomes 1 and 5 also decreased blood pressure, protein excretion, and albumin excretion. These studies also identified several chromosomes in male (6, 11, Y) and female (4, 6, 11, 19, 20) rats that reduced albuminuria without altering blood pressure. These data indicate that genes contributing to salt-sensitive hypertension are found on multiple chromosomes of the Dahl SS/Mcwi rat. Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats.

Author List

Mattson DL, Dwinell MR, Greene AS, Kwitek AE, Roman RJ, Jacob HJ, Cowley AW Jr

Authors

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin
Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Catheterization
Chromosome Mapping
Disease Models, Animal
Hypertension
Kidney Diseases
Male
Phenotype
Rats
Rats, Inbred Dahl
Sex Factors
Sodium Chloride, Dietary