Pex3 is involved in the genetic regulation of Nr3c2 expression in the amygdala of mice

Abstract

The mineralocorticoid receptor (Nr3c2) has received increased attention as an important stress-related gene. Here, we sought to uncover candidate genes regulating the expression of Nr3c2. Using a genetical genomics approach, we identified a significant trans-regulated expression quantitative trait locus (eQTL) at Chromosome 10 for Nr3c2 expression in the amygdala of BXD RI strains. We then examined genes upstream of the eQTL to identify likely regulatory candidates of Nr3c2 expression. Pex3 (peroxisomal) expression was highly correlated with that of Nr3c2, had a significant cis-regulated eQTL that mapped to the Nr3c2 eQTL region and thus emerged as the most likely regulatory candidate of Nr3c2 expression. In vitro studies showed that silencing of Pex3 by siRNA decreased Nr3c2 expression in HEK293T and SHSY5 cell lines while overexpression increased Nr3c2 expression. A relationship between the expression of these two genes was further supported by our observations that expression levels of Pex3 and Nr3c2 decreased in the amygdala of mice exposed to chronic unpredictable stress. Our findings provide insight into the genetic regulation of Nr3c2 expression and suggest a new role for Pex3 in stress responses. Future characterization of Pex3's role in the regulation of Nr3c2 expression and the pathways involved may lead to a better understanding of stress responses and risk for stress-related pathology.

Keywords: Amygdala; Chronic unpredictable stress; Expression quantitative trait locus (eQTL); Nr3c2; Pex3.