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Molecular and Cellular Biology, September 2002, p. 6605-6610, Vol. 22, No. 18
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.18.6605-6610.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Urocortin-Deficient Mice Display Normal Stress-Induced Anxiety Behavior and Autonomic Control but an Impaired Acoustic Startle Response

Xiaozhong Wang,¹ Hong Su,¹ Leslie D. Copenhagen,¹ Sukishi Vaishnav,¹ Fredalina Pieri,² Cynthia Do Shope,³ William E. Brownell,³ Mariella De Biasi,² Richard Paylor,^1,2 and Allan Bradley^1,4*

Department of Molecular and Human Genetics,¹ Division of Neuroscience,² Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas 77030,³ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom⁴

Received 24 January 2002/ Returned for modification 25 February 2002/ Accepted 24 June 2002

Corticotropin-releasing hormone (Crh) plays an important role in modulating physiological and behavioral responses to stress. Its actions are mediated through two receptors, Crhr1 and Crhr2. Urocortin (Ucn), a Crh-related neuropeptide and the postulated endogenous ligand for Crhr2, is a potential mediator of stress responses. We generated Ucn-deficient mice using embryonic stem cell technology to determine its role in stress-induced behavioral and autonomic responses. Unlike Crhr1- or Crhr2-deficient mice, Ucn-deficient mice exhibit normal anxiety-like behavior as well as autonomic regulation in response to stress. However, the mutant mice display an impaired acoustic startle response that is not due to an obvious hearing defect. Thus, our results suggest that Ucn does not play an essential role in stress-induced behavioral and autonomic responses. Ucn may modulate the acoustic startle response through the Ucn-expressing neuron projections from the region of the Edinger-Westphal nucleus.

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* Corresponding author. Mailing address: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom. Phone: 01223 834244. Fax: 01223 494919. E-mail: abradley{at}sanger.ac.uk.

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Molecular and Cellular Biology, September 2002, p. 6605-6610, Vol. 22, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.18.6605-6610.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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