Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress.
Nat Genet. 2000-04-01; 24(4): 410-414
DOI: 10.1038/74263
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1. Nat Genet. 2000 Apr;24(4):410-4.
Mice deficient for corticotropin-releasing hormone receptor-2 display
anxiety-like behaviour and are hypersensitive to stress.
Bale TL(1), Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, Koob GF, Vale
WW, Lee KF.
Author information:
(1)Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La
Jolla, CA
Corticotropin-releasing hormone (Crh) is a critical coordinator of the
hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released
from the paraventricular nucleus (PVN) of the hypothalamus activates Crh
receptors on anterior pituitary corticotropes, resulting in release of
adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates
Acth receptors in the adrenal cortex to increase synthesis and release of
glucocorticoids. The receptors for Crh, Crhr1 and Crhr2, are found throughout the
central nervous system and periphery. Crh has a higher affinity for Crhr1 than
for Crhr2, and urocortin (Ucn), a Crh-related peptide, is thought to be the
endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity
than does Crh. Crhr1 and Crhr2 share approximately 71% amino acid sequence
similarity and are distinct in their localization within the brain and peripheral
tissues. We generated mice deficient for Crhr2 to determine the physiological
role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display
increased anxiety-like behaviour. Mutant mice have normal basal feeding and
weight gain, but decreased food intake following food deprivation. Intravenous
Ucn produces no effect on mean arterial pressure in the mutant mice.
DOI: 10.1038/74263
PMID: 10742108 [Indexed for MEDLINE]