Ectopic Expression of Oryx (Oryx dammah) Prion Protein Induces Disturbance in Cardiac Rhythms and Dilated Spongiform Cardiomyopathy

Cellular prion protein (PrP^C) is a host protein anchored to the outer surface of neurons and, to a lesser extent, lymphocytes. The transmissible agent (PrP^Sc) responsible for scrapie is believed to be a modified form of PrP^C. However, the physiological role of PrP^C in normal, uninfected animals remains unknown. Here, we describe a novel mouse model of dilated cardiomyopathy (DCM) observed during the development of prion agent-susceptible transgenic (Tg) mice. These Tg mice selectively express scimitar-horned oryx (Oryx dammah) PrP (OrPrP) in their tissues, as demonstrated by RT-PCR for mRNA, Western blotting, and immunohistochemistry. High levels of OrPrP expression were detected in the heart, moderate levels in skeletal muscle, low levels in the brain, and barely detectable levels in the lung, liver, spleen, kidney, and thymus. Notably, electrocardiogram (ECG) analysis revealed that cardiac muscle contraction was significantly prolonged, with abnormalities in the QRS interval. Additionally, histological examination showed multiple intracytoplasmic vacuolations in the heart muscle. These findings suggest that high expression of OrPrP in the heart may contribute to cardiac abnormalities. Furthermore, an abnormal ECG waveform was observed in these Tg mice following atropine injection. This mouse model may provide a valuable tool for studying experimental DCM.