B6-hPCSK9 (CDS) mice are generated by integrating the human PCSK9 protein coding sequence (CDS) and 3' untranslated region (UTR) into the mouse Pcsk9 gene locus using gene editing techniques, resulting in a model expressing human PCSK9 protein while disrupting the expression of the mouse endogenous Pcsk9 gene. These mice can be used to study various metabolic diseases, neurodegenerative diseases, tumor development, and autoimmune diseases, as well as for the development, screening, and preclinical pharmacological evaluation of PCSK9-targeted drugs. Compared to the similar B6-hPCSK9 mice (PCSK9 genomic humanized model, Catalog Number: C001617), B6-hPCSK9 (CDS) mice have higher levels of human PCSK9 protein expression in serum, while LDLR expression is closer to the normal endogenous levels in mice.