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

COX-1(-/-)小鼠健康，无明显病理改变。 COX-1(-/-)幼崽按预期比例出生。值得注意的是，在 COX-1(-/-)小鼠，COX-2在某些组织中表达上调， 在几个组织的蛋白质水平上显著上调。 从机制上讲，这种上调必须是补偿性的，并表明 之前未知的COX-1和COX-2之间的串扰方式。 COX-1(-/-)小鼠减少巨噬细胞产生PGE-2，减少 ERTEA引起的血小板聚集和炎症反应减弱 化学物质；但悬而未决的是，非甾体抗炎药引起的胃溃疡 相当于COX-1(+/+)小鼠。COX-1(-/-)女性有生育能力/分娩 问题取决于雄性和/或幼崽的基因。的研究 COX-2基因敲除的小鼠比COX-1小鼠处于早期阶段；但 在NIEHS和北卡罗来纳大学都在进行中。与COX-1小鼠相比，COX-2(-/-) 老鼠通常是不健康的，100%的老鼠在5个月前死亡 (病理正在确定)。因此，通过利用这些小鼠 我们可以对炎症过程有更好的了解 一般，COX-1和COX-2在炎症性疾病中的具体作用， 以及关于COX-1和COX-2在 致癌过程。此外，这一知识将使 设计更好的治疗和预防炎症的药物 疾病。

COX-1(-/-) mice are of normal health and show no obvious pathology. COX-1(-/-) pups are born in the expected ratio. Significantly, in COX-1(-/-) mice, COX-2 message is upregulated in some tissues and is greatly upregulated at the protein level in several tissues. Mechanistically, this upregulation must be compensatory and indicates a means of crosstalk between COX-1 and COX-2 which was previously unknown. COX-1(-/-) mice have reduced PGE-2 production by macrophages, reduced platelet aggregation and reduced inflammatory response to ertain chemicals; but susprisingly, NSAID induced gastric ulceration is about equal to COX-1(+/+) mice. COX-1(-/-) females have fertility/partuition problems dependent on the genotype of the male and/or pups. Studies of the COX-2 knock-out are at an earlier stage than the COX-1 mice; but are in progress both at NIEHS and UNC. By contrast to COX-1 mice COX-2(-/-) mice are generally unhealthy with 100% dying before 5 months of age (pathologies are being determined). Therefore, by utilizing these mice we can gain a better understanding of the inflammatory process in general, the specific roles of COX-1 and COX-2 in inflammatory diseases, as well as insight concerning the roles of COX-1 and -2 in the carcinogenesis process. Additionally, this knowledge will allow the design of better therapeutic and prophylatic drugs to treat inflammatory diseases.