Chromosomal substitution affects the severity of ischemia‐induced acute renal failure in BN and SS rats

Abstract

This study sought to determine the potential location of alleles in the Brown-Norway (BN/Mcw) genome required for resistance to renal ischemia/reperfusion (I/R) injury. We compared BN/Mcw rats, Dahl S (SS/Mcw) rats and rats derived from these two strains in response to 40 min I/R. SS/Mcw rats were significantly injured as indicated by serum creatinine rising from 0.4±0.1 mg/dl pre-surgery to 3.0 ± 0.6 mg/dl at 24 hours of reperfusion and also histological evidence of tubular damage. In contrast, the rise in serum creatinine values in BN/Mcw was significantly less (0.8 ± 0.1 mg/dl) and there was little evidence of tubular damage. F1 generation rats derived from a BN/Mcw X SS/Mcw were injured to an equivalent degree as parental SS/Mcw rat, regardless of which strain was maternal. We then tested the sensitivity to renal I/R in consomic rat strains derived by introgressing chromosomes of the BN/Mcw rat into the SS/Mcw background. Of 17 consomic rat strains evaluated, 15 manifested substantial injury with mean serum creatinine values ranging between 2.5 and 4.3 mg/dl at 24 hours post surgery. In contrast, two consomic rat strains demonstrated an apparent resistance to renal I/R injury; these were the SS-BN8 and SS-BN5 (BN/Mcw chromosome 8 and 5 on SS/Mcw background). Mean serum creatinine values were 1.4 ± 0.2 and 1.8 ± 0.6 mg/dl at 24 hours post-ischemia, respectively. These data suggest that protection in the BN rat is primarily the result of autosomal recessive alleles likely residing on either chromosome 8 and/or 5 of the BN/Mcw genome.