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Identification of eQTLs for hepatic Xbp1s and Socs3 gene expression in mice fed a high-fat, high-caloric diet.

Pasricha S, Kenney-Hunt J, Anderson K, Jafari N, Hall RA, Lammert F, Cheverud J, Green RM - G3 (Bethesda) (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina.

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Hepatic mRNA expression of Xbp1s and Socs3 in A/J, C57BL/6J, and C57BL/6J-Chr 1A/J/NaJ and C57BL/6J-Chr 11A/J/NaJ mice. Male A/J, C57BL/6J, C57BL/6J-Chr 1A/J/NaJ, and C57BL/6J-Chr 11A/J/NaJ mice were fed a 60% high-fat, high-caloric (HFHC) diet for 8 wk and hepatic mRNA expression of (A) Xbp1s and (B) Socs3 gene expression measured using RT-PCR. RLU, random light units. Mean ± SEM. A/J (white), C57BL/6J (black), C57BL/6J-Chr 1A/J/NaJ (Chr 1, light gray), and C57BL/6J-Chr 11A/J/NaJ (Chr 11, dark gray). ap < 0.05 vs. both C57BL/6J and C57BL/6J-Chr 1A/J/NaJ mice (n = 8).
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fig4: Hepatic mRNA expression of Xbp1s and Socs3 in A/J, C57BL/6J, and C57BL/6J-Chr 1A/J/NaJ and C57BL/6J-Chr 11A/J/NaJ mice. Male A/J, C57BL/6J, C57BL/6J-Chr 1A/J/NaJ, and C57BL/6J-Chr 11A/J/NaJ mice were fed a 60% high-fat, high-caloric (HFHC) diet for 8 wk and hepatic mRNA expression of (A) Xbp1s and (B) Socs3 gene expression measured using RT-PCR. RLU, random light units. Mean ± SEM. A/J (white), C57BL/6J (black), C57BL/6J-Chr 1A/J/NaJ (Chr 1, light gray), and C57BL/6J-Chr 11A/J/NaJ (Chr 11, dark gray). ap < 0.05 vs. both C57BL/6J and C57BL/6J-Chr 1A/J/NaJ mice (n = 8).

Mentions: Because eQTLs for both Xbp1s and Socs3 were identified on chromosomes 1 and 11, we performed RT-PCR of Xbp1s and Socs3 on hepatic mRNA isolated from C57BL/6J-Chr 1A/J/ NaJ and C57BL/6J-Chr 11A/J/ NaJ CSS mice, and a new cohort of A/J and C57BL/6J mice, fed the HFHC diet for 8 wk. Hepatic gene expression of Xbp1s was 1.0 ± 0.2 and 0.6 ± 0.2 in A/J and C57BL/6J-Chr 11A/J/ NaJ mice, and 0.3 ± 0.2 and 0.2 ± 0.2 in C57BL/6J and C57BL/6J-Chr 1A/J/ NaJ mice (Figure 4). Therefore, Xbp1s gene expression was higher in C57BL/6J-Chr 11A/J/ NaJ mice than in C57BL6/J mice (P < 0.05), but was similar in C57BL/6J-Chr 1A/J/ NaJ mice and C57BL/6 mice. Replacement of A/J chromosome 11, but not chromosome 1, into strain C57BL/6 mice reversed the Xbp1s phenotype. Hepatic Socs3 gene expression was similar (1.0 ± 0.2 and 1.0 ± 0.2 RLU) in A/J and C57BL/6J-Chr 11A/J/ NaJ mice, but was also lower in both the C57BL/6J and C57BL/6J-Chr 1A/J/ NaJ mice, at 0.5 ± 0.2 and 0.5 ± 0.2 RLU, respectively (P < 0.05; n = 8). Transfer of A/J chromosome 11, but not chromosome 1, into C57BL/6J mice reversed the Socs3 phenotype, similar to the findings of hepatic Xbp1s mRNA expression.


Identification of eQTLs for hepatic Xbp1s and Socs3 gene expression in mice fed a high-fat, high-caloric diet.

Pasricha S, Kenney-Hunt J, Anderson K, Jafari N, Hall RA, Lammert F, Cheverud J, Green RM - G3 (Bethesda) (2015)

Hepatic mRNA expression of Xbp1s and Socs3 in A/J, C57BL/6J, and C57BL/6J-Chr 1A/J/NaJ and C57BL/6J-Chr 11A/J/NaJ mice. Male A/J, C57BL/6J, C57BL/6J-Chr 1A/J/NaJ, and C57BL/6J-Chr 11A/J/NaJ mice were fed a 60% high-fat, high-caloric (HFHC) diet for 8 wk and hepatic mRNA expression of (A) Xbp1s and (B) Socs3 gene expression measured using RT-PCR. RLU, random light units. Mean ± SEM. A/J (white), C57BL/6J (black), C57BL/6J-Chr 1A/J/NaJ (Chr 1, light gray), and C57BL/6J-Chr 11A/J/NaJ (Chr 11, dark gray). ap < 0.05 vs. both C57BL/6J and C57BL/6J-Chr 1A/J/NaJ mice (n = 8).
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fig4: Hepatic mRNA expression of Xbp1s and Socs3 in A/J, C57BL/6J, and C57BL/6J-Chr 1A/J/NaJ and C57BL/6J-Chr 11A/J/NaJ mice. Male A/J, C57BL/6J, C57BL/6J-Chr 1A/J/NaJ, and C57BL/6J-Chr 11A/J/NaJ mice were fed a 60% high-fat, high-caloric (HFHC) diet for 8 wk and hepatic mRNA expression of (A) Xbp1s and (B) Socs3 gene expression measured using RT-PCR. RLU, random light units. Mean ± SEM. A/J (white), C57BL/6J (black), C57BL/6J-Chr 1A/J/NaJ (Chr 1, light gray), and C57BL/6J-Chr 11A/J/NaJ (Chr 11, dark gray). ap < 0.05 vs. both C57BL/6J and C57BL/6J-Chr 1A/J/NaJ mice (n = 8).
Mentions: Because eQTLs for both Xbp1s and Socs3 were identified on chromosomes 1 and 11, we performed RT-PCR of Xbp1s and Socs3 on hepatic mRNA isolated from C57BL/6J-Chr 1A/J/ NaJ and C57BL/6J-Chr 11A/J/ NaJ CSS mice, and a new cohort of A/J and C57BL/6J mice, fed the HFHC diet for 8 wk. Hepatic gene expression of Xbp1s was 1.0 ± 0.2 and 0.6 ± 0.2 in A/J and C57BL/6J-Chr 11A/J/ NaJ mice, and 0.3 ± 0.2 and 0.2 ± 0.2 in C57BL/6J and C57BL/6J-Chr 1A/J/ NaJ mice (Figure 4). Therefore, Xbp1s gene expression was higher in C57BL/6J-Chr 11A/J/ NaJ mice than in C57BL6/J mice (P < 0.05), but was similar in C57BL/6J-Chr 1A/J/ NaJ mice and C57BL/6 mice. Replacement of A/J chromosome 11, but not chromosome 1, into strain C57BL/6 mice reversed the Xbp1s phenotype. Hepatic Socs3 gene expression was similar (1.0 ± 0.2 and 1.0 ± 0.2 RLU) in A/J and C57BL/6J-Chr 11A/J/ NaJ mice, but was also lower in both the C57BL/6J and C57BL/6J-Chr 1A/J/ NaJ mice, at 0.5 ± 0.2 and 0.5 ± 0.2 RLU, respectively (P < 0.05; n = 8). Transfer of A/J chromosome 11, but not chromosome 1, into C57BL/6J mice reversed the Socs3 phenotype, similar to the findings of hepatic Xbp1s mRNA expression.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Northwestern University, Chicago, Illinois Department of Internal Medicine, University of North Carolina, Chapel Hill, North Carolina.

Show MeSH
Related in: MedlinePlus