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

工作总结：一系列项目正在进行中 用环氧合酶（考克斯）基因敲除小鼠。1)肿瘤发生 在考克斯-1和考克斯-2无效菌株中， DMBA/TPA两阶段皮肤模型和Apc（min）突变体 肠息肉病模型。皮肤乳头状瘤形成减少 与对照组相比，两种敲除菌株中均降低了70%。 这似乎是由于几个稳态因素的改变， 包括表皮复制和细胞凋亡的速率。考克斯-1和 将考克斯-2小鼠培育成APC（min）小鼠， 易患自发性结肠腺息肉病。的 任何一种考克斯亚型的缺乏都通过以下途径减少结肠癌的发生： 在这个背景下，80%。2)使用气囊模型， 炎症，考克斯-1和-2反应的差异 已经观察到小鼠对炎性化学试剂的反应， PGE 2的产生，以及募集的细胞的数量和类型。 3)已经产生了考克斯-1和考克斯-2缺陷的小鼠。 这些小鼠，以及只携带一个单一拷贝的小鼠， 考克斯基因，正被用来确定的生理作用， 单个考克斯同种型。

Summary of Work: A series of projects are ongoing with the cyclooxygenase (COX) knock-out mice. 1) Tumorigenesis in the COX-1 and COX-2 null strains has been studied using the DMBA/TPA two stage skin model and the Apc (min) mutant intestinal polyposis model. Skin papilloma formation was reduced by 70% in both of the knockout strains compared to the control. This appears to be due to alterations in several homeostatic factors, including rates of epidermal replication and apoptosis. COX-1 and COX-2 mice have been bred to APC (min) mice which are susceptible to spontaneous adenopolyposis of the colon. The deficiency of either COX isoform reduces colon carcinogenesis by about 80% in this background. 2) Using the air pouch model for inflammation, differences in the responses of the COX-1 and -2 mice to inflammatory chemical agents have been observed in production of PGE2, and in the number and type of cells recruited. 3) Mice deficient in both COX-1 and COX-2 have been produced. These mice, and mice carrying only a single copy of one of the COX genes, are being used to determine the physiological roles of the individual COX isoforms.