Identification of eQTLs for Hepatic Xbp1s and Socs3 Gene Expression in Mice Fed a High-Fat, High Caloric Diet

Authors

James M. Cheverud, Loyola University ChicagoFollow
Sarina Pasricha, Northwestern University
Jane Kenney-Hunt, Westminster College - Fulton
Kristy Anderson, Northwestern University
Naderah Jafari, Northwestern University
Rabea A. Hall, Saarland University Medical Center
Frank Lammert, Saarland University Medical Center
Richard M. Green, Northwestern University

Document Type

Article

Publication Date

2015

Publication Title

G3: Genes, Genomes, Genetics

Volume

5

Issue

4

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 11A/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 1A/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 Socs3on 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 andSocs3 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.

Comments

Author Posting. © 2015, the authors. This article is posted here by permission of the authors for personal use, not for redistribution. The article was published in G3: Genes, Genomes, Genetics, Volume 5, Issue 4, 2015, http://dx.doi.org/10.1534/g3.115.016626

Recommended Citation

Chevered, J. et al. "Identification of eQTLs for Hepatic Xbp1s and Socs3 Gene Expression in Mice Fed a High-Fat, High Caloric Diet." G3: Genes, Genomes, Genetics 5(4), 2015.

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Copyright Statement

© 2015, the authors.