Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice.
Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stress-induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased "free" CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.
Karolyi
I J
IJ
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA.
Burrows
H L
HL
Ramesh
T M
TM
Nakajima
M
M
Lesh
J S
JS
Seong
E
E
Camper
S A
SA
Seasholtz
A F
AF
D000818:Animals; D001007:Anxiety / Q000209:etiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D010913:Pituitary-Adrenal System / Q000502:physiology; D015430:Weight Gain
D002352:Carrier Proteins; C067133:corticotropin releasing factor-binding protein