title: Identification of eQTLs for hepatic Xbp1s and Socs3 gene expression in mice fed a high-fat, high-caloric diet.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of human hepatic disease and feeding mice a high-fat, high-caloric (HFHC) diet is a standard model of NAFLD. To better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. Two-hundred sixty-five (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 wk. eQTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1s and Socs3 on Chr 1 (164.0-185.4 Mb and 174.4-190.5 Mb, respectively) and Chr 11 (41.1-73.1 Mb and 44.0-68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9-117.4 Mb). C57BL/6J-Chr 11(A/J)/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (P < 0.05), whereas C57BL/6J-Chr 1(A/J)/ NaJ mice retained the C57BL/6J phenotype. In addition, we replicated the eQTLs on Chr 1 and Chr 12 (LOD scores ≥3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and Chr 11, and consomic mice confirmed that replacing the C57BL/6J Chr 11 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases.
authors.affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sarina
authors.initials: S
authors.lastname: Pasricha
authors.affiliation: Department of Biology and Environmental Science, Westminster College, Fulton, Missouri.
authors.forename: Jane
authors.initials: J
authors.lastname: Kenney-Hunt
authors.affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Kristy
authors.initials: K
authors.lastname: Anderson
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
authors.forename: Rabea A
authors.initials: RA
authors.lastname: Hall
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.affiliation: Department of Biology, Loyola University, Chicago, Illinois.
authors.forename: James
authors.initials: J
authors.lastname: Cheverud
authors.affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois r-green2@northwestern.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Green
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D002875:Chromosomes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D040641:Quantitative Trait Loci; D000071701:Regulatory Factor X Transcription Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; D002251:Carbon Tetrachloride
keywords: eQTLs; fatty; liver; mice