Characterization of transgenic mouse models for Arhythmogenic Right Ventricular Cardiomyopathy

To verify that the overexpression of the transgene (human DSG2) did not lead to any alteration in myocardium, two lines of transgenic wild-type mice were used as controls. The two lines differ for number of integrated copies of transgene; In particular while WT11 line has picked up in his genome only 2 copies of transgene, WT 40 may function as exclusive control, because has integrated a number of transgene copies comparable with other transgenic lines (approximately 40). Offspring of the two different founders were then studied in order to estimate if different level of expression of h-DSG2 influenced the phenotype. We have performed a gross morphological examination of the hearts from WT11-Tg mice of 11 months of age; Azan Mallory, hematoxylin-eosin (H&E), and von Kossa staining of heart sections did not reveal any pathological change in these mice. In order to verify that the obtained result were not due to the few number of integrated copies of the transgene, we have performed the same studies on the hearts of mice of WT40 line. Also for WT40 mice, Azan Mallory, hematoxylin-eosin (H&E), and von Kossa staining of heart sections did not reveal any pathological change (Figure 8). To be confident that a so high number of copies of transgene doesn’t lead to a disease-like phenotype it will be important to study older WT40 mice. This results permit us to speculate that structural abnormalities observed in transgenic lines could be linked to mutation introduced and not to overexpression of human desmoglein-2.