Voltage-dependent Ca_V1.2 L-type calcium channels play a critical role in the regulation blood pressure. Besides, Ca_V1.2 is implicated to play a pivotal role in chronic vessel remodeling such as atherosclerosis because several clinical trials indicate that Ca_V1.2 inhibitors delay the progression of atherosclerosis. However, how Ca_V1.2 participates in atherogenesis still remains obscure. Vascular smooth muscle cells (VSMC) are critically involved in atherogenesis. Medial VSMCs migrate and proliferate into the intima and form a part of plaque upon endothelial injury. Recently, we have identified that two tyrosine residues in the C-terminus (Tyr1709 and Tyr1758) of VSMC Ca_V1.2 are phosphorylated by Src-family kinases in response to PDGF. In vitro studies demonstrated that PDGF enhances Ca_V1.2 channel activity through this phosphorylation, thereby induceing VSMC migration. Thus, Ca_V1.2 may contribute to vessel remodeling in atherosclerosis. In order to verify this hypothesis, we established a knock-in mice line harboring a mutation at one of the tyrosine residues (Y1709F by using the CRISPR/Cas9 system. Although these mice exhibited no obvious developmental defects, we are now analyzing the effect of carotid artery ligation, a model of intimal thickening in these mice.