Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-7-24
pubmed:abstractText
Corticotropin releasing factor (CRF) is a major integrator of adaptive responses to stress. Two biochemically and pharmacologically distinct CRF receptor subtypes (CRFR1 and CRFR2) have been described. We have generated mice null for the CRFR1 gene to elucidate the specific developmental and physiological roles of CRF receptor mediated pathways. Behavioral analyses revealed that mice lacking CRFR1 displayed markedly reduced anxiety. Mutant mice also failed to exhibit the characteristic hormonal response to stress due to a disruption of the hypothalamic-pituitary-adrenal (HPA) axis. Homozygous mutant mice derived from crossing heterozygotes displayed low plasma corticosterone concentrations resulting from a marked agenesis of the zona fasciculata region of the adrenal gland. The offspring from homozygote crosses died within 48 hr after birth due to a pronounced lung dysplasia. The adrenal agenesis in mutant animals was attributed to insufficient adrenocorticotropic hormone (ACTH) production during the neonatal period and was rescued by ACTH replacement. These results suggest that CRFR1 plays an important role both in the development of a functional HPA axis and in mediating behavioral changes associated with anxiety.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0896-6273
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1093-102
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9655498-Adaptation, Physiological, pubmed-meshheading:9655498-Adrenal Gland Diseases, pubmed-meshheading:9655498-Adrenal Glands, pubmed-meshheading:9655498-Adrenocorticotropic Hormone, pubmed-meshheading:9655498-Animals, pubmed-meshheading:9655498-Anxiety, pubmed-meshheading:9655498-Behavior, Animal, pubmed-meshheading:9655498-Chimera, pubmed-meshheading:9655498-Corticosterone, pubmed-meshheading:9655498-Female, pubmed-meshheading:9655498-Gene Expression Regulation, Developmental, pubmed-meshheading:9655498-Homozygote, pubmed-meshheading:9655498-Male, pubmed-meshheading:9655498-Maze Learning, pubmed-meshheading:9655498-Mice, pubmed-meshheading:9655498-Mice, Inbred C57BL, pubmed-meshheading:9655498-Mice, Neurologic Mutants, pubmed-meshheading:9655498-Mutation, pubmed-meshheading:9655498-Neurosecretory Systems, pubmed-meshheading:9655498-Paraventricular Hypothalamic Nucleus, pubmed-meshheading:9655498-Pituitary Gland, pubmed-meshheading:9655498-Receptors, Corticotropin-Releasing Hormone, pubmed-meshheading:9655498-Stress, Physiological, pubmed-meshheading:9655498-Survival Analysis
pubmed:year
1998
pubmed:articleTitle
Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development.
pubmed:affiliation
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't