[Frontiers in Bioscience 11, 2876-2888, September 1, 2006]

Cyclooxygenase 2: understanding the pathophysiological role through genetically altered mouse models

Paloma Martin Sanz 1, 2, Sonsoles Hortelano 2, Lisardo Bosca 1, 2 and Marta Casado 3

1 Centro de Investigaciones Biologicas CIB (CSIC), 2 Centro Nacional de Investigaciones Cardiovasculares (CNIC). Melchor Fernandez Almagro 3, 28029 Madrid, Spain, 3Instituto de Biomedicina de Valencia (CSIC) Jaime Roig 11, 46010 Valencia, Spain


1. Abstract
2. Introduction
3. Insight into the physiological roles of COX-2 through genetically altered mice
3.1. Kidney
3.2. Gastrointestinal tract
3.3. Reproduction
3.4. Brain
3.5. Cardiovascular system
3.6. Liver
4. COX-2 in pathological states
4.1. Inflammation
4.2. Tumorigenesis
4.2.1. Gastric and intestinal tumors
4.2.2. Breast cancer
4.2.3. Skin carcinogenesis
4.2.4. Hepatocellular carcinoma (HCC)
5. Summary and Perspectives
6. Acknowledgement
7. References


Cyclooxygenase (COX) -1 and -2 catalyze the first step in the biosynthesis of prostanoids. COX-1 is constitutively expressed in many tissues and seems to be involved in the housekeeping function of prostanoids. COX-2, the inducible isoform, accounts for the elevated production of prostaglandins in response to various inflammatory stimuli, hormones and growth factors. COX-2 expression has been also associated with cell growth regulation, tissue remodelling and carcinogenesis. More of these characteristics have been elucidate through using COX selective inhibitors. Recent advances in transgenic and gene-targeting approaches allow a sophisticated manipulation of the mouse genome by gene addition, gene deletion or gene modifications. The development of COX-2 genetically altered mice has provided models to elucidate the physiological and pathophysiological roles of this enzyme.