title: Genetic regulatory network analysis reveals that low density lipoprotein receptor-related protein 11 is involved in stress responses in mice.
abstract: To study whether Lrp11 is involved in stress response and find its expression regulatory network, the model of stress has been built using C57BL/6J (B6) and DBA/2 (D2) mice. Western blotting, qPCR and immunohistochemistry were used to investigate the expression variation of Lrp11 in amygdala tissue after exposure to stress. We found the quantity of Lrp11 was more obvious in stress models than that in normal mice (P<0.05) which suggests Lrp11 might participate in the process of stress response. The expression of Lrp11 is controlled by a cis-acting quantitative trait locus (cis-eQTL). We identified four genes that are regulated by Lrp11 and the expression of 66 genes highly correlated with Lrp11, seven of which have previously been implicated in stress pathways. To evaluate the relationship between Lrp11 and its downstream genes or network members, we transfected HEK 293T cells and SH-SY5Y cells with Lrp11 siRNA leading to down-regulation of Lrp11mRNA and were able to confirm a significant influence of Lrp11 depletion on the expression of Xpnpep1, Maneal, Pgap1 and Uprt. These validated downstream targets and members of Lrp11 gene network provide new insight into the biological role of Lrp11 and may be an important risk factor in the development of 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 Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Jiangsu, Nantong 226001, China.
authors.forename: Rixin
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Jiangsu, Nantong 226001, China.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Dongjian
authors.initials: D
authors.lastname: Chen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Jiangsu, Nantong 226001, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of neurology, Affiliated Hospital of Nantong University, Jiangsu, Nantong 226001, China.
authors.forename: Maohong
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Histology and Embryology, Medical College, Nantong University, Jiangsu, Nantong 226001, China. Electronic address: yingchen00034@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D053263:Gene Regulatory Networks / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D026502:LDL-Receptor Related Proteins
keywords: Amygdala; Expression quantitative trait locus (eQTL); Gene network; Lrp11; Stress