Phosphoprotein Enriched in Astrocytes (PEA15) is a 15kD-sized intracellular signaling protein, highly expressed in astrocytes and constitutively expressed in peripheral tissues. Recently it was found that PEA15 expression was elevated in patients suffering type 2 diabetes and suggested to be involved in the syndrome of insulin resistance. To investigate the functional role of PEA15 for the control of blood glucose level, we produced a transgenic pig over-expressing mouse PEA15 (mPEA15). As a model animal, pig has many advantages. They have a higher fecundity and a short generation time and are physiologically similar to human. Using the transgenic pig, we carried out a series of experiments to establish a link between PEA15 expression and the insulin resistance. Our results suggested that, compared with control pig, mPEA15 pig has, (1) a higher blood resistin level, (2) a lower cell membrane-embeded GLUT4 level, and (3) a lower glucose clearing ability based on oral glucose tolerance test (OGTT). When our results combined, it can be concluded that mPEA15 over-expressing pig has many symptoms of insulin resistance and these pigs will become a useful disease model to investigate diabetes mellitus in the near future.

The overexpression of Phosphoprotein Enriched in Astrocytes (PEA15) gene is commonly found in human diabetic patients. The overexpression of this gene in skeletal muscle and fat tissues have been reported to cause insulin resistance, thereby impairing insulin stimulated glucose uptake. We introduced a gene of mouse PEA15 (mPEA15) and enhanced green fluorescent protein (EGFP) into fertilized one cell pig zygotes using microinjection, and produced a piglet that showed overexpression of mPEA15 in the muscle tissues and expression of EGFP in the ear tissues and hooves. RT-PCR RFLP, southern blot and FISH analysis showed that the tissues carried the transgene. Real-time RT-PCR and western blots demonstrated that PEA15 gene was overexpressed in the various tissues and muscle tissues, respectively. These facts suggest that expression vector system is normally expressed in the trnasgenic (TG) pigs. To use as animal diseases model for type 2 diabetes, further study is necessary to confirm whether diabetes occur in these TG pigs, especially insulin resistance.