Mouse corticotropin-releasing factor receptor type 2α gene: Isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids

Effects of the corticotropin-releasing factor (CRF) family of peptides are mediated through activation of two receptors, CRF receptor (CRFR) 1 and CRFR2. Based on the homology between known mammalian CRFR genes, we have isolated a cDNA encoding the mouse CRFR2α (mCRFR2α) ortholog from brain. The isolated cDNA encodes a 411-amino acid protein with high identity to the rat (∼97%) and human (∼93%) receptors. Central and peripheral expression of mCRFR2α, determined by RT-PCR followed by Southern hybridization, revealed that mCRFR2α is restricted mainly to brain structures, with highest levels in the hypothalamus and olfactory bulb. In situ hybridization showed mCRFR2α localization in discrete brain regions, including the lateral septum and the ventromedial hypothalamus, whereas mCRFR2β is found only in the choroid plexus. Binding and signaling of CRF-related ligands was studied using COS-M6 or HEK293T cells transiently transfected with mCRFR2α. Urocortins (Ucns) show different affinities for binding to mCRFR2...