Site-specific overexpression of corticotropin-releasing hormone (CRH) in the mouse brain – modelling central CRH system hyperactivity

To gain deeper insight into the consequences of corticotropin-releasing hormone (CRH) system hyperactivity, as observed in human affective disorders including major depression, we generated a mouse model which allows the conditional CRH overexpression from the ROSA26 locus (COR). Combining the knock-in of the murine CRH cDNA into the ROSA26 locus with the Cre/loxP system enabled us to overexpress CRH in a spatially regulated fashion at different dosages. Initially we established a mouse line where CRH overexpression is restricted to the central nervous system (CNS, COR-Nes). We will present data on the fundamental analysis of COR-Nes mice including molecular characterization, endocrinology and basic emotionality. Initial pharmacological validation demonstrates that COR-Nes mice might not only serve as a suitable model to study the consequences of chronic CRH hyperactivity but could also present a versatile tool for the identification and validation of effective CRH-R1 antagonists.