Genetic expression analysis of E2F-associated phosphoprotein in stress responses in the mouse.

Dysfunction of the monoaminergic system is critical in stress and anxiety disorders, but the role of each family member in the development of stress-related psychopathologies is not sufficiently understood. Eapp has been reported to be a transcriptional repressor of monoamine oxidase B (Maob) and down-regulates Maob via the Maob core promoter. In the present study, we more specifically examine the role of Eapp in stress responses by testing the hypothesis that Eapp may be involved in the occurrence and development of stress responses. Western blotting, qPCR and immunohistochemistry were used to investigate the expression variation of Eapp in hypothalamus tissue after exposure to stress. The expression of Eapp is controlled by a cis-acting quantitative trait locus (cis-eQTL). Two genes Sphk2 and Nosip, had trans-eQTLs that mapped to the location of Eapp and altered expression of these two genes was shown following siRNA knockdown of Eapp. Additionally, Mmp9, Npy, Npy5r and Maob were shown to have different expression levels in the Eapp knock-down experiments. Our data provide strong evidence that the cis-modulated gene, Eapp, is associated with stress responses, and that validated downstream targets and members of Eapp gene network may also be involved in the development of stress.