Ectopic Expression of Oryx (<em>Oryx dammah</em>) Prion Protein Induces Disturbance in Cardiac Rhythms and Dilated Spongiform Cardiomyopathy; Oryx PrP Gene Introduction Enhances the Doppel Gene Expression in Murine Myocardium

Cellular prion protein (PrPC) is a host protein anchored to the outer surface of neurons and, to a lesser extent, to lymphocytes. The transmissible agent (PrPSc), the causative agent for scrapie, is believed to be a modified form of PrPC. However, the role of PrPC in normal, uninfected animals remains unknown. Here, we describe a novel mouse model for dilated cardiomyopathy (DCM), which was observed during the development of pri-on-agent-susceptible transgenic mice (Tg mice). Tg mice were shown to selectively express scimitar-horned oryx (Oryx dammah) PrP (OrPrP) in their tissues, as demonstrated through RT-PCR for mRNA, Western blotting, and immunohistochemistry. High levels of OrPrP expression were observed in the heart, medium levels in the skeletal muscle, low levels in the brain, and barely detectable levels in the lung, liver, spleen, kidney, and thymus. Elec-trocardiogram (ECG) findings showed significantly prolonged cardiac muscle contraction, with abnormalities in the QRS interval. Additionally, histological analysis showed multi-ple intracytoplasmic vacuolation in the heart muscle. Furthermore, an abnormal ECG waveform of was observed in Tg mice following atropine injection. These mice may pro-vide a new model for analyzing experimental DCM. Besides, the Tg mice showed higher expression levels of OrPrP in the heart muscle following increased Doppel (Dpl) gene ex-pression. Overexpression of Dpl gene may occur in the myocardium, controlled by OrPrP. These findings suggest that higher expression of OrPrP and Dpl gene in the heart may cause cardiac abnormalities. In the histopathological studies of myocardium, the cyto-plasmic vacuolation of muscle fibers were seen both in Tg(OrPrP)Prnp+/+ and Tg(OrPrP)Prnp0/0 mice, but not in C57BL/6J mice.