Intrinsic expression of transcortin in neural cells of the mouse brain: a histochemical and molecular study

Abstract

Summary Corticosteroid binding globulin (CBG, transcortin) has been shown to be expressed in the brain of rat and human species. In this study we examined the CBG brain expression and cDNA structure in mice, comparing wild-type (Cbg+/+) and Cbg knockout mice (Cbg-/-, obtained by genetic disruption of the SerpinA6 alias Cbg gene). We used double immunofluorescence labelling with specific neuronal and glial markers to analyze the cellular localization of CBG in various regions of the mouse brain. In wild-type (Cbg+/+) mice we found CBG immunoreactivity in neuronal perikarya of the magnocellular hypothalamic nuclei, amygdala, hippocampus, cerebral cortex, cerebellum and pituitary. A portion of glial cells (astrocytes, oligodendrocytes) contained CBG immunoreactivity, including some of the ependymal cells and choroid plexus cells. No CBG immunoreactivity was detected in Cbg-/- brain tissues. We showed by RT-PCR that the full-length Cbg mRNA is present in those regions, indicating an intrinsic expression of the steroid-binding globulin. Furthermore, we found by sequencing analysis that Cbg cDNA obtained from the mouse hypothalamus was homologous to Cbg cDNA obtained from the liver. Finally, we have evaluated the relative levels of CBG expression by quantitative PCR in various brain regions and in the liver. We found that brain levels of Cbg mRNA are low compared to the liver but significantly higher than in CBG-deficient mice. Although derived from the same gene than liver CBG, brain CBG protein may play a specific or complementary role that requires the production and analysis of brain-specific Cbg knockout models.