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Understanding corticotropin releasing factor neurobiology: contributions from mutant mice
A Contarino1, S C Heinrichs, L H Gold
1Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA.
Abstract:
Mice with transgenic expression or deletion of the CRF peptide, transgenic expression of the CRF-BP or deletion of specific CRF receptor subtypes exist and will be valuable for examining candidate mediators in animal model systems recapitulating a variety of normal function. In particular, results described in this review implicate CRF in acute emotional responses studied in animal models of anxiety and drug abstinence. CRF also appears to play a role in behavioral and physiological plasticity judging by alterations in HPA reactivity to stress, information processing and energy balance regulation in CRF mutant models. Accordingly, the creation of genetically engineered mice now permits the evaluation of contributory roles for several CRF-related gene products in the pathophysiology of a variety of complex behavioral disorders. For example, the postulated causal linkage between overactivation of CRF systems and the hyper-emotionality which characterizes human affective disorders can now be more thoroughly evaluated by examining the phenotype of CRF mutant mice in animal models of depression, dementia and substance abuse.
Insights
Genetically engineered mouse models with altered corticotropin-releasing factor (CRF) systems are crucial for studying emotional responses and stress-related disorders. These models help investigate CRF
Area of Science:
- Neuroscience
- Genetics
- Behavioral Science
Background:
- Corticotropin-releasing factor (CRF) systems are implicated in stress responses and emotional regulation.
- Existing genetically engineered mouse models offer valuable tools for studying CRF's role.
Purpose of the Study:
- To review the utility of genetically modified mouse models in understanding CRF's function.
- To explore the involvement of CRF in anxiety, drug abstinence, and affective disorders.
Main Methods:
- Utilizing transgenic mice with altered CRF peptide, CRF-binding protein (CRF-BP), or CRF receptor subtypes.
- Examining phenotypes in animal models of anxiety, drug abstinence, depression, dementia, and substance abuse.
Main Results:
- CRF is implicated in acute emotional responses, including anxiety and drug abstinence.
- CRF influences behavioral and physiological plasticity, affecting HPA axis reactivity, information processing, and energy balance.
- Genetically engineered mice facilitate the evaluation of CRF-related gene products in behavioral disorder pathophysiology.
Conclusions:
- Genetically engineered mouse models are essential for dissecting the role of CRF in normal function and disease.
- These models enable thorough evaluation of the link between CRF system overactivation and human affective disorders.