Objective To construct a mouse model with mammary tissue?specific modification of the BRCA1, BRCA2, and CDH1 genes using the CRISPR/ Cas9 system. Methods Single?stranded RNAs (sgRNAs) targeting the exons of the mouse BRCA1, BRCA2, and CDH1 genes were designed and synthesized, and the biological function of each sgRNA was validated in HEPA cells. Three sgRNAs were successively linked to the pX330?spCas9?U6?gRNA coexpression vector, and the CBh promoter was replaced by the mammary tissue?specific promoter WAP. The obtained final vector was linearized by the restriction endonuclease SbfI, after which it was injected into mouse zygotes to generate transgenic mice. Results A total of 190 zygotes were injected and 130 positive zygotes were implanted into four recipient mice. There were 42 offspring of F0 mice, while 11 mice were identified to have modified transgenes; the positive rate of transgenic mice was 26. 19%. A total of 39 F1 mice were obtained by F0 generation breeding and 9 F1 transgenic mice were detected. Conclusions Transgenic mice were successfully generated by constructing a mammary tissue?specific coexpression vector.