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

工作总结：一系列阐明单个环氧合酶（考克斯）异构体生理功能的项目正在考克斯基因敲除小鼠中进行。1)使用DMBA/TPA两阶段皮肤模型和Apc（min）突变小鼠研究了COX 1和COX 2缺失株中的肿瘤发生。在这两种肿瘤发生模型中，与对照组相比，COX 1和COX 2缺陷小鼠的肿瘤形成减少了75%。这似乎是由于几个稳态因子的改变，包括细胞复制，分化和凋亡。2)正在使用可注射的B16-F1细胞研究对考克斯基因敲除小鼠中可移植肿瘤生长的影响。肿瘤大小和发病在COX 1缺失小鼠中有所减少，在COX 2缺失小鼠中基本上减少。3)已经产生了COX 1和COX 2两者缺陷的小鼠。这些小鼠和仅携带一个考克斯基因拷贝的小鼠被用于确定单个考克斯同种型的生理作用。两种亚型缺陷的小鼠在动脉导管未闭出生后不久死亡。此外，还观察到几个内脏器官的发育缺陷。- 环氧合酶，考克斯，ptgs，结肠，皮肤，前列腺素，肿瘤发生

Summary of Work: A series of projects to elucidate the physiological functions of the individual cyclooxygenase (COX) isoforms are ongoing with the COX knockout mice. 1) Tumorigenesis in the COX1 and COX2 null strains has been studied using the DMBA/TPA two stage skin model and the Apc (min) mutant mice. Tumor formation was reduced by 75% in both COX1 and COX2 deficient mice compared to the controls in both of these tumorigenesis models. This appears to be due to alterations in several homeostatic factors, including cell replication, differentiation and apoptosis. 2) Effects on transplantable tumor growth in the COX null mice are being studied using injectable B16-F1 cells. Tumor size and onset are reduced somewhat in the COX1 null mice and substantially in the COX2 null mice. 3) Mice deficient in both COX1 and COX2 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. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus. In addition, developmental defects in several internal organs are observed. - cyclooxygenase, cox, ptgs, colon, skin, prostaglandin, tumorigenesis