Progeny of mice crossed with a Myh6-tTA strain are not viable unless doxycycline (DOX) is administered. Double transgenic animals not treated with DOX develop severe dilated cardiomyopathy and die between 4-8 weeks of age. In the presence of DOX, a greater than 50% loss of SYPL2 expression is seen in the heart. This lower expression of SYPL2 protein in the DOX-treated animals localizes to t-tubules adjacent to RYR2 (ryanodine receptor 2, cardiac) in the apposing SR.