title: Increased susceptibility to kidney injury by transfer of genomic segment from SHR onto Dahl S genetic background.
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.
authors.affiliation: Department of Medicine (Nephrology), Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Regner
authors.forename: Ashlyn C
authors.initials: AC
authors.lastname: Harmon
authors.forename: Jan M
authors.initials: JM
authors.lastname: Williams
authors.forename: Cary
authors.initials: C
authors.lastname: Stelloh
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Johnson
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Kyle
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lerch-Gaggl
authors.forename: Sarah M
authors.initials: SM
authors.lastname: White
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garrett
mesh_terms: D000818:Animals; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D007668:Kidney / Q000293:injuries*; D007674:Kidney Diseases / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D015996:Survival Rate