Faculty Collaboration Database

Increased susceptibility to kidney injury by transfer of genomic segment from SHR onto Dahl S genetic background. Physiol Genomics 2012 Jun 15;44(12):629-37

Date

05/03/2012

Pubmed ID

22548739

Pubmed Central ID

PMC3426430

DOI

10.1152/physiolgenomics.00015.2012

Scopus ID

2-s2.0-84862628928 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

The Dahl salt-sensitive (S) rat is a widely studied model of salt-sensitive hypertension and develops proteinuria, glomerulosclerosis, and renal interstitial fibrosis. An earlier genetic analysis using a population derived from the S and spontaneously hypertensive rat (SHR) identified eight genomic regions linked to renal injury in the S rat and one protective locus on chromosome 11. The "protective" locus in the S rat was replaced with the SHR genomic segment conferring "susceptibility" to kidney injury. The progression of kidney injury in the S.SHR(11) congenic strain was characterized in the present study. Groups of S and S.SHR(11) rats were followed for 12 wk on either a low-salt (0.3% NaCl) or high-salt (2% NaCl) diet. By week 12 (low-salt), S.SHR(11) demonstrated a significant decline in kidney function compared with the S. Blood pressure was significantly elevated in both strains on high salt. Despite similar blood pressure, the S.SHR(11) exhibited a more significant decline in kidney function compared with the S. The decline in S.SHR(11) kidney function was associated with more severe kidney injury including tubular loss, immune cell infiltration, and tubulointerstitial fibrosis compared with the S. Most prominently, the S.SHR(11) exhibited a high degree of medullary fibrosis and a significant increase in renal vascular medial hypertrophy. In summary, genetic modification of the S rat generated a model of accelerated renal disease that may provide a better system to study progression to renal failure as well as lead to the identification of genetic variants involved in kidney injury.

Author List

Regner KR, Harmon AC, Williams JM, Stelloh C, Johnson AC, Kyle PB, Lerch-Gaggl A, White SM, Garrett MR

Author

Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of Wisconsin

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

Animals
Genetic Linkage
Genetic Predisposition to Disease
Kidney
Kidney Diseases
Proteinuria
Rats
Rats, Inbred Dahl
Rats, Inbred SHR
Survival Rate