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Chromosome substitution modulates resistance to ischemia reperfusion injury in Brown Norway rats. Kidney Int 2013 Feb;83(2):242-50 PMID: 23235564 PMCID: PMC3561482

Pubmed ID

23235564

Abstract

Brown Norway rats (BN, BN/NHsdMcwi) are profoundly resistant to developing acute kidney injury (AKI) following ischemia reperfusion. To help define the genetic basis for this resistance, we used consomic rats, in which individual chromosomes from BN rats were placed into the genetic background of Dahl SS rats (SS, SS/JrHsdMcwi) to determine which chromosomes contain alleles contributing to protection from AKI. The parental strains had dramatically different sensitivity to ischemia reperfusion with plasma creatinine levels following 45 min of ischemia and 24 h reperfusion of 4.1 and 1.3 mg/dl in SS and BN, respectively. No consomic strain showed protection similar to the parental BN strain. Nine consomic strains (SS-7(BN), SS-X(BN), SS-8(BN), SS-4(BN), SS-15(BN), SS-3(BN), SS-10(BN), SS-6(BN), and SS-5(BN)) showed partial protection (plasma creatinine about 2.5-3.0 mg/dl), suggesting that multiple alleles contribute to the severity of AKI. In silico analysis was performed using disease ontology database terms and renal function quantitative trait loci from the Rat Genome Database on the BN chromosomes giving partial protection from AKI. This tactic identified at least 36 candidate genes, with several previously linked to the pathophysiology of AKI. Thus, natural variants of these alleles or yet-to-be identified alleles on these chromosomes provide protection against AKI. These alleles may be potential modulators of AKI in susceptible patient populations.

Author List

Basile DP, Dwinell MR, Wang SJ, Shames BD, Donohoe DL, Chen S, Sreedharan R, Van Why SK

Authors

Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin




Scopus

2-s2.0-84873411495   9 Citations

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

Acute Kidney Injury
Animals
Chromosomes, Mammalian
Creatinine
DNA-Binding Proteins
Genetic Predisposition to Disease
Heat Shock Transcription Factors
Quantitative Trait Loci
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Reperfusion Injury
Transcription Factors
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3