Identification of eQTLs for hepatic Xbp1s and Socs3 gene expression in mice fed a high-fat, high-caloric diet.
Bottom Line: 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).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.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.
Affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina.Show MeSH
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Mentions: Parental mouse strains C57BL/6J and A/J fed a HFHC diet for 8 wk elicited significant differences in the hepatic gene expression of Xbp1s: 1.0 ± 0.2 vs. 0.4 ± 0.2 in A/J and C57BL/6J mice, respectively (P < 0.05). There was also a similar difference in hepatic Socs3 gene expression: 1.0 ± 0.2 vs. 0.6 ± 0.2 in A/J and C57BL/6J mice, respectively (P < 0.05). Hepatic Xbp1s and Socs3 gene expression in F1 (A/J × C57BL/6J) mice was 0.7 ± 0.1 for Xbp1s and 0.7 ± 0.2 for Socs3 (P < 0.05), both significantly different from A/J mice. Hepatic Xbp1s expression also differed between the F1 (A/J × C57BL/6J) and C57BL/6J mice (Figure 1; n = 8 for all groups). Supporting Information, Table S1 shows the Pearson correlation matrix of the phenotypes Xbp1s and Socs3 in C57BL/6J and A/J mice (as well as for several phenotypes of the metabolic syndrome).
Affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina.