Impact of Animal Strain on Gene Expression in a Rat Model of Acute Cardiac Rejection

ABSTRACT: The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR). Additional analysis allowed for selection of 49 candidate genes uniquely associated with ACR, but only after accounting for the unexpectedly large effect of animal strain. Studies of ACR that examine gene expression in peripheral blood may be confounded by strain differences. These results indicate the need for study designs that eliminate or control for the large effect of genetic background on the transcriptome of immune cells. Using a rat heart transplant model microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC). Total RNA was isolated, reverse transcribed, labeled, and hybridized to oligonucleotide microarrays. In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ï?³ 3). Only 13 genes were affected by both strain and rejection, which was < 1% (13/1368) of all probesets differentially expressed in ACR. However, for PBMCs, strain alone affected 265 probesets (FDR 10% and FC ï?³ 3) and the addition of ACR had little further effect. Pathway analysis of strain effect in PBMCs associated gene expression differences with immune response, cell motility and cell death, functional themes that overlap with those related to ACR.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Hao Chen 

PROVIDER: E-GEOD-6342 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress