MOUSE MODEL--TARGETED GENE KNOCK-OUT OF PROSTAGLANDIN SYNTHASE I AND II

工作概述：一系列项目正在进行中的环氧合酶 (COX)敲除小鼠 1)COX 1和COX 2缺失株中的肿瘤发生 使用DMBA/TPA两阶段皮肤模型进行了研究。乳头瘤 在两种敲除菌株中， 控制。 NSAID对肿瘤发生的影响也正在研究中。 研究并与淘汰赛的效果进行比较。2)气囊具有 在考克斯-1和考克斯-2敲除小鼠上成功形成。他们的 正在研究对炎性物质（角叉菜胶和TPA）的反应。 考克斯-1和-2动物的反应差异已被证实。 在PGE 2和LTB 4的产生中观察到， 炎症的部位。3)将考克斯-1和考克斯-2小鼠培育成APC (min)对自发性腺息肉病易感的小鼠， 结肠基因敲除对自发性结肠癌发生的影响 将在不存在或存在NSAID的情况下进行研究。 4)考克斯-1和 将考克斯-2敲除物培育到C57/BL 6 J和129 J近交系中。 这些小鼠将为未来的研究提供一个同质的遗传背景。 研究，并应导致改善所有研究的统计数据。

Summary of Work: A series of projects are ongoing in the cyclooxygenase (COX) knockout mice. 1) Tumorigenesis in the COX1 and COX2 null strains has been studied using the DMBA/TPA two stage skin model. Papilloma formation was reduced by 60% in both of the knockout strains compared to the control. The effects of NSAIDs on tumorigenesis are also being studied and compared to the effects of the knockouts. 2) Air pouchs have been successfully formed on the COX-1 and COX-2 knockout mice. Their responses to inflammatory agents (carageenan and TPA) are being studied. Differences in the responses of the COX-1 and -2 animals have been observed in production of PGE2 and LTB4, and in the cells recruited to the site of inflammation. 3) COX-1 and COX-2 mice are being bred to APC (min) mice which are susceptible to spontaneous adenopolyposis of the colon. The effects of the knockouts on spontaneous colon carcinogenesis will be studied in the absence or presence of NSAIDs. 4) The COX-1 and COX-2 knockouts are being bred into the C57/BL6J and 129J inbred strains. These mice will provide a homogenous genetic background for future studies and should lead to improved statistics in all studies.