Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity.
Our previous work found DA rats superior for intrinsic aerobic running capacity (ARC) and several cardiac function indexes compared with Copenhagen (COP) rats, and identified ARC quantitative trait loci (QTLs) on rat chromosomes 16 (RNO16) and 3 (RNO3). The purpose of this study was to use these inbred rat strains as a genetic substrate for differential cardiac gene expression to identify candidate genes for the observed ARC QTLs. RNA expression was examined globally in left ventricles of 15-wk-old DA, F1(COP x DA), and COP rats using microarrays to identify candidate genes for ARC QTLs. We identified 199 differentially expressed probe sets and determined their chromosomal locations. Six differentially expressed genes and expressed sequence tags (ESTs) mapped near ARC QTL regions, including PDZ and LIM domain 3 (Pdlim3). Differential expression of these genes/ESTs was confirmed by quantitative RT-PCR. The Ingenuity Pathways program identified 13 biological networks containing 50 (of the 199) differentially expressed probe sets and 85 additional genes. Four of these eighty-five genes mapped near ARC QTL-containing regions, including insulin receptor substrate 2 (Irs2) and acyl-CoA synthetase long-chain family member 1 (Acsl1). Most (148/199) differentially expressed probe sets showed left ventricular expression patterns consistent with the alleles exerting additive effects, i.e., F1(COP x DA) rat RNA expression was intermediate between DA and COP rats. This study identified several potential ARC QTL candidate genes and molecular networks, one of them related to energy expenditure involving Pik3r1 mRNA expression that may, in part, explain the observed strain differences in ARC and cardiac performance.
Lee
Soon Jin
SJ
Department of Physiology and Cardiovascular Genomics, Medical University of Ohio, Toledo, Ohio 43614, USA. sjlee@meduohio.edu
Ways
Justin A
JA
Barbato
John C
JC
Essig
David
D
Pettee
Krista
K
DeRaedt
Sarah J
SJ
Yang
Siming
S
Weaver
David A
DA
Koch
Lauren G
LG
Cicila
George T
GT
D000818:Animals; D002874:Chromosome Mapping; D016000:Cluster Analysis; D003066:Coenzyme A Ligases / Q000378:metabolism; D004195:Disease Models, Animal; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D005810:Multigene Family; D009206:Myocardium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010805:Physical Conditioning, Animal; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012420:Running; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526299:Irs2 protein, rat; D009841:Oligonucleotides; D010750:Phosphoproteins; D012333:RNA, Messenger; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase