Wang Xiaozhong, Su Hong, Copenhagen Leslie D, Vaishnav Sukishi, Pieri Fredalina, Shope Cynthia Do, Brownell William E, De Biasi Mariella, Paylor Richard, Bradley Allan
Department of Molecular and Human Genetics, Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Mol Cell Biol. 2002 Sep;22(18):6605-10. doi: 10.1128/MCB.22.18.6605-6610.2002.
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.
促肾上腺皮质激素释放激素（Crh）在调节对应激的生理和行为反应中起重要作用。其作用通过两种受体Crhr1和Crhr2介导。尿皮质素（Ucn）是一种与Crh相关的神经肽，被认为是Crhr2的内源性配体，是应激反应的潜在介质。我们利用胚胎干细胞技术培育出Ucn缺陷型小鼠，以确定其在应激诱导的行为和自主反应中的作用。与Crhr1或Crhr2缺陷型小鼠不同，Ucn缺陷型小鼠在应激反应中表现出正常的焦虑样行为以及自主调节。然而，突变小鼠表现出听觉惊吓反应受损，这并非由明显的听力缺陷所致。因此，我们的结果表明，Ucn在应激诱导的行为和自主反应中不发挥重要作用。Ucn可能通过来自动眼神经核区域的表达Ucn的神经元投射来调节听觉惊吓反应。
