Generation of a CRH-Cre mouse line to analyze the CRH system

The establishment of site-specific recombinases such as Cre, Flp and fC31 has revolutionized mouse genetics by providing means to delete, insert, invert, or exchange chromosomal DNA with high fidelity (for review see: Nagy, 2000). The available genetic toolbox favours the mouse as the ideal model organism to functionally approach gene function and to model human disease. To specifically target CRH expressing neurons we are currently generating transgenic mice, which will express conventional and inducible Cre-recombinase under the control of the CRH promotor. To achieve this goal we applied Red/ET-cloning techniques and BAC/Fosmid transgenesis in order to guarantee a Cre-recombinase expression matching the endogenous pattern of CRH expression. Random integration of the CRH-Cre constructs has been performed by pronucleus injection and transfection of embryonic stem cells. First transgenic founders have been obtained and transgenic offspring will be characterized. Established Cre lines will be bred with conditional CRH overexpressing mice in order to model central CRH hyperdrive as observed in patients with major depression. Moreover, these Cre mice could prove as extremely useful for analyzing CRH signaling pathways in vivo.