Identification of eQTLs for Hepatic Xbp1s and Socs3 Gene Expression in Mice Fed a High-Fat, High-Caloric Diet. Issue 4 (1st April 2015)

• Record Type: Journal Article
• Authors: Pasricha, Sarina; Kenney-Hunt, Jane; Anderson, Kristy; Jafari, Nadereh; Hall, Rabea A; Lammert, Frank; Cheverud, James; Green, Richard M
• Is Part Of: G3. Volume 5:Issue 4(2015)
• Page Start: 487
• Page End: 496
• Publication Date: 2015-04-01
• Subjects: eQTLs -- mice -- fatty -- liver; Genetics -- Research -- Periodicals; Genomics -- Periodicals; Genetics; Genomics; Genes; Genetics -- Research; Genomics; Electronic journals; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; 572.8
• DOI: 10.1534/g3.115.016626
• Languages: English
• ISSNs: 2160-1836

Abstract

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.