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

工作概述：一系列阐明COX基因敲除小鼠环氧化酶（COX）亚型生理功能的项目正在进行中。1)采用DMBA/TPA两期皮肤模型和Apc （min）突变小鼠研究了COX1和COX2零株的肿瘤发生。在这两种肿瘤发生模型中，COX1和COX2缺陷小鼠的肿瘤形成都比对照组减少了75%。这似乎是由于几个稳态因素的改变，包括细胞复制、分化和凋亡。2)利用可注射的B16-F1细胞研究对COX缺失小鼠可移植肿瘤生长的影响。COX1缺失小鼠的肿瘤大小和发病程度有所降低，COX2缺失小鼠的肿瘤大小和发病程度显著降低。3)已经产生了COX1和COX2都缺乏的小鼠。这些小鼠，以及只携带一个COX基因拷贝的小鼠，被用来确定单个COX亚型的生理作用。缺乏这两种亚型的小鼠在动脉导管未闭出生后不久死亡。此外，还观察到一些内脏器官的发育缺陷。-环氧化酶，cox, 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