Taconic
273 Hover Ave.
Germantown, NY, 12526-5320
Website: http://www.taconic.com
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COX Targeted Mutation Models
Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) Targeted Mutation Mouse models are offered for investigating the role of cyclooxygenases in inflammatory diseases. COX Targeted Mutation mice have disruptions in one of the two Pts (protaglandin-endoperoxide synthase) genes. In the COX-1 mouse model the Ptgs 1 gene is disrupted, resulting in an absence of the catalyst cyclooxygenase-1. In contrast, the gene Ptgs2 is disrupted in the COX-2 mouse, resulting in an absence of cyclooxygenase-2 catalyst. The primary function of cyclooxygenases is to convert arachidonic acid to prostaglandin H2 (PGH2, the rate-limiting step of prostaglandin synthesis. Prostaglandins control the inflammatory response and proper development of precursors of the T cells, or thymocytes. Researching the function of cyclooxygenases benefits the development of more accurate NSAIDS, drugs designed to reduce inflammation, and advances studies of the immune system. Together, the two mouse models can be used to elucidate the role of cyclooxygenase in prostaglandin synthesis. The models can also reveal the compensatory nature of the two genes Ptgs1 and Ptgs2, since the catalysts COX-1 and COX-2 are isoforms with overlapping functions. COX-1 Targeted Mutation Mice reveal no physical differences compared to wild-type mice. Upon gross and microscopic examination, organ systems appear normal and healthy. Characteristics of the COX-1 model include reduced platelet aggregation, decreased sensitivity of the early-phase inflammatory response, altered thymocyte development, and increased susceptibility to injury of the colon and death from the chemical irritant dextran sodium sulfate (DSS). Additionally, while female mice show normal fertility, the mortality rates of their offspring are high. In comparison, organ systems in COX-2 mice appear normal and healthy, with the exception of the kidneys. Characteristics of the model include altered development of thymocytes, increased vulnerability of the colonic mucosa to DSS compared to both wild-type and COX-1 mice, and lack of response of the immune system to lipopolysaccharide. Also in contrast to COX-1 mice, homozygous female COX-2 mice are infertile. The average lifespan of COX-2 mice is also eight weeks shorter compared to wild-type mice.
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