To investigate the effect of α-Syn phosphorylation in a physiologically relevant context, we used CRISPR-Cas9 to edit the endogenous mouse Snca gene and develop phosphomimetic α-Syn knock-in (KI) mouse models containing single phosphorylation sites, Y39E and S129D, which are hyperphosphorylated in PD patients. This evidence concerns the gene SNCA and Parkinson disease.