Generation and Characterization of Coupling Factor 6-Overexpressing Transgenic Mice

概要

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We showed that endogenous prostacyclin inhibitor coupling factor 6 （CF6） is released from vascularendothelial cells and its release is stimulated by tumor necrosis factor-α, which is related to congestive heart failure（CHF）. We also showed that CF6 increases the gene expression related to CHF. To investigate the role of CF6 inthe genesis of CHF, we generated CF6-overexpressing transgenic（ TG） mice, and characterized the phenotype. DNAfragment consisting of human elongation factor 1α promoter, and human calcitonin/CF6 fused gene was injected intothe embryo of C57BL/6J mouse, and homozygous TG mice were generated. In TG mice, CF6 gene was overexpressedby two fold in overall tissues compared with wild type（ WT） mice. Under normal salt diet, blood pressure, heart rate,and the expression of energy metabolism-related genes were similar between TG and WT mice. When the mice werefed with 8% -salt diet for 35 weeks, the mortality of TG mice was higher than that of WT mice（ survival rate; 50% inTG versus 92% in WT, p<0.05 by log-rank test）. This preliminary report indicates that further examination, especiallyanalysis of the cardiac function, is needed to clarify the cause of high mortality of TG mice under high salt intake.
弘前大学の論文