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Ectopic calcification in the cardiovascular system adversely affects life prognosis. DBA/2 mice experience calcification owing to low expression of Abcc6 as observed in pseudoxanthoma elasticum (PXE) patients; however, little is known about its characteristics as a calcification model. In this study, we explore the suitability of a DBA/2 sub-strain as a PXE-like tissue calcification model, and the effect of a bisphosphonate which prevents calcification of soft tissues in hypercalcemic models was evaluated. The incidence of calcification of the heart was compared among several sub-strains and between both sexes of DBA/2 mice. mRNA expression of calcification-related genes was compared with DBA/2 sub-strains and other mouse strains. In addition, progression of calcification and calciprotein particle formation in serum were examined. Among several sub-strains of DBA/2 mice, male DBA/2CrSlc mice showed the most remarkable cardiac calcification. In DBA/2CrSlc mice, expression of the anti-calcifying genes Abcc6, Enpp1 and Spp1 was lower than that in C57BL/6J, and expression of Enpp1 and Spp1 was lower compared with other sub-strains. Calcification was accompanied by accelerated formation of calciprotein particle, which was prevented by daily treatment with bisphosphonate. A model suitable for ectopic calcification was identified by choosing a sub-strain of DBA/2 mice, in which genetic characteristics would contribute to extended calcification.