NF-KAPPA BS IN VIVO ROLE IN DERMATITIS AND ANGIOGENESIS

描述（来自应用程序）： 多效性转录因子NF-κ B是转录因子的主要成分。 免疫反应和炎症。 一些基因参与了 血管生成和白细胞血管外化（VEGF，VEGF受体，VCAM， ICAM、ELAM）被认为受NF-κ B调节或含有NF-κ B 启动子中的结合位点。 然而，这些数据中的绝大多数 都是通过体外系统积累起来的 众所周知，在 体外系统可能不能准确地描绘体内事件。 为了 研究NF-kappaB在体内的作用，这项资助提出了以下建议： 1)IkappaB α缺乏者皮炎发生的研究 小鼠 在该动物模型中，IkappaB α基因已经通过以下途径被删除： 同源重组 这些动物发展出一种严重的广泛传播的 皮炎在生命的第一周。 这种皮炎的发展是 在出生后3至6天发生的时间上可预测的，这将 允许对皮炎的发展进行阶段性研究。 具体地说， 血管内皮生长因子及其靶点的表达将 在表达的时间和空间模式方面进行研究。 其他可能参与皮炎的基因，如基质蛋白酶， 追究 2)开发四环素诱导/抑制系统， 利用NF-κ B相关基因的皮肤炎症模型 系统 预计这些模型还将允许 研究者直接控制皮炎和其他 允许研究空间和时间基因的炎症性疾病 如上所述的表达。 此外，这些动物可以作为资源 用于药物开发和筛选，因为它们将代表更明确的 实验系统 一旦四环素诱导/抑制系统 已经被开发用于皮肤研究，它们可以被进一步利用， 开发其他疾病的动物模型。

DESCRIPTION (from the application): The pleiotropic transcription factor NF-kappaB is a major component of the immune response and inflammation. Several of the genes involved in angiogenesis and leukocyte evascularization (vegf, vegf receptor, VCAM, ICAM, ELAM) are thought to be regulated by NF-kappaB or contain NF-kappaB binding sites in their promoters. However, the vast majority of these data have been accumulated using in vitro systems. It is well known, that in vitro systems may not accurately portray in vivo events. In order to investigate NF-kappaB's role in vivo, this grant proposes the following: 1) Study of the development of dermatitis in the IkappaBalpha deficient mice. In this animal model, the IkappaBalpha gene has been deleted via homologous recombination. These animals develop a severe wide-spread dermatitis in the first week of life. The development of this dermatitis is temporally predictable occurring between 3 to 6 days after birth, which will allow for a staged study of the development of dermatitis. Specifically, the expression of vascular endothelial growth factors and their targets will be investigated in terms of the temporal and spatial pattern of expression. Other genes potentially involved in dermatitis such as matrix proteases will be investigated. 2) Develop the tetracycline inducible/repressible systems to create animal models of dermal inflammation exploiting the genes involved in the NF-kappaB system. It is anticipated that these models will also allow the investigator to directly control the onset of dermatitis and other inflammatory diseases allowing the study of spatial and temporal gene expression as discussed above. Further, these animals may serve as resource for drug development and screening as they will represent a more defined experimental system. Once the tetracycline inducible/repressible systems have been developed for cutaneous study, they can be further exploited to develop animal models for other diseases.