title: Genetic regulation analysis reveals involvement of tumor necrosis factor and alpha-induced protein 3 in stress response in mice.
abstract: In order to study whether Tnfaip3 is related to stress response and further to find it's genetic regulation, we use C57BL/6J (B6) and DBA/2 (D2) mice to built the model of chronic unpredictable mild stress. RT-PCR, Western blotting and immunohistochemistry were used for studying the expression variation of Tnfaip3 in hippocampus tissue of B6 and D2 mice after being stressed. We found that the expression of Tnfaip3 was more remarkably increased in chronic unpredictable stress models than that in untreated mice (P<0.05). It is indicated that Tnfaip3 might take part in the process of stress response. The expression of Tnfaip3 is regulated by a cis-acting quantitative trait locus (cis-eQTL). We identified 5 genes are controlled by Tnfaip3 and the expression of 64 genes highly associated with Tnfaip3, 9 of those have formerly been participate in stress related pathways. In order to estimate the relationship between Tnfaip3 and its downstream genes or network members, we transfected SH-SY5Y cells with Tnfaip3 siRNA leading to down-regulation of Tnfaip3 mRNA. We confirmed a significant influence of Tnfaip3 depletion on the expression of Tsc22d3, Pex7, Rap2a, Slc2a3, and Gap43. These validated downstream genes and members of Tnfaip3 gene network provide us new insight into the biological mechanisms of Tnfaip3 in chronic unpredictable stress.
authors.affiliation: Department of Neurology, Nantong University Affiliated Mental Health Center, Jiangsu, Nantong 226001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Dai
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China. Electronic address: cmhongnt@sina.com.
authors.forename: Maohong
authors.initials: M
authors.lastname: Cao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D040641:Quantitative Trait Loci; D013312:Stress, Physiological / Q000235:genetics*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse
keywords: Expression quantitative trait locus(eQTL); Gene network; Hippocampus; Stress; Tnfaip3