Research Development Foundation

Tracy L Bale

Wylie Walker Vale, Jr

Kuo-Fen Lee

George W Smith

The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2 (CRFR2). Mice deficient for CRFR1 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.

Method of inhibiting angiogenesis by administration of a corticotropin releasing factor receptor 2 agonist

The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2. Corticotropin releasing factor is a critical integrator of the hypothalamic-pituitary-adrenal axis in response to stress. CRF and its related molecule urocortin bind CRF receptor 1 and CRFR2 with distinct affinities. CRFR2 mutant mice were hypersensitive to stress and displayed increased anxiety-like behavior. Mutant mice had normal basal feeding and weight gain, but exhibited decreased food intake following food deprivation. Intravenous UCN dramatically decreased the mean arterial pressure in the controls but had no effect in the mutants. A deficiency of CRFR2 results in a significant increase in urocortin mRNA in the rostral region of the Edinger Westphal and a significant increase in CRF mRNA in central nucleus of the amygdala. These results demonstrate that the CRFR2 mutant mice, opposed to CRFR1 mutant mice, have an increased sensitivity to stress and display anxiety-like behavior. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis.

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San Diego, CA, United States of America

Tracy L Bale