Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression in the liver of ethanol-treated mice via gastric tube in multiple strains


ABSTRACT: This study tested a hypothesis that a population-based approach may identify genetic background-dependent and -independent genes/pathways that modulate alcohol-induced liver injury. A sub-chronic (4 weeks) intra-gastric alcohol infusion (up to 27 g/kg/day) model was used to control for alcohol intake in 15 genetically diverse inbred mouse strains. Urine, serum and liver markers of alcoholic steato-hepatitis were assessed and a wide range of liver damage was observed across the panel. Gene expression profiling was performed on liver tissue collected at the end of the study and statistical models, with strain, degree of liver injury, treatment, and their interaction terms as factors, were used to select transcripts associated with strain-dependent and -independent effects of alcohol on the liver. Translational control of hepatic protein synthesis, related to eukaryotic initiation factors (eiFs) and accessory proteins, was identified as genetic background-independent mode of alcohol-induced liver injury. Interestingly, immune response-related transcription factors signal transducer and activator of transcription 1 (Stat1) and nuclear factor, interleukin 3 regulated (Nfil3/E4bp4) are likely determinants of genetic background-dependent responses to liver injury and alcohol treatment, respectively. Our data demonstrate that a multistrain approach provides critical mechanistic information for understanding genetic factors influencing alcohol toxicity and facilitate identification of novel targets of therapeutic intervention. A high-fat diet or EtOH-containing high-fat diet was administered to 15 strains of mice via gastric tube for 28 days. 3 replicates per strain/diet. Inter-batch normalization was carried out using the ComBat procedure. The supplementary file 'GSE20052_Readme.txt' contains a description of the replicates used for normalization. The 'GSE20052_US14702406_25148681*' files linked to the GSE20052 record are the raw data files for the replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Ivan Rusyn 

PROVIDER: E-GEOD-20052 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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