CORTICOTROPIN RELEASING FACTOR RECEPTOR 2 DEFICIENT MICE AND USES THEREOF

摘要

The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2 (CRFR2). Mice deficient for CRFRI exhibit decreased anxiety-like behavior and a decreased stress response. In contrast, CRFR2 null mutant mice are hypersensitive to stress and display increased anxiety-like behavior. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis. CRFR2 null mutant mice also exhibit increased angiogenesis in all tissues examined. Thus, CRFR2 antagonists may be used to stimulate angiogenesis for the treatment of various conditions. In contrast, CRFR2 agonists may be used to inhibit angiogenesis. A combination of urocortin and bFGF was observed to stimulate rapid hair growth. The CRFR2 mutant mice are also useful for the study of the effects of CRFR2 deficiency on homeostatic responses to stress, including a high-fat diet, repeated cold stress, and glucose and insulin challenges. The mutant mice to such stresses enable methods to screen compounds for effects on homeostasis, which are useful in screening compounds to provide treatments for pathological conditions related to the regulation of homeostasis, including obesity and type 2 diabetes.