The CRISPR/Cas9 System. A. General CRISPR/Cas9 system; in the general CRISPR/Cas9 system, Cas9/sgRNA complex recognizes the complementary 20-nucleotide genomic sequence with a downstream protospacer-adjacent motif (PAM) sequence; it cuts three nucleotides upstream of the PAM sequence to induce double-strand DNA breaks (DSBs); the DSBs are then repaired through two major mechanisms: NHEJ pathway which is usually for knock-out genes and HDR pathway which is usually for knock- in genes. B. CRISPR/Cas9 transgenic mouse model; CRISPR/Cas9 germline transgenic mouse models are generated by injecting Cas9 mRNA with one or multiple single guide RNAs (sgRNA) directly into mouse germline embryos; two kinds of mouse genome modifications will occur: constitutive knock-out tumor suppressor genes through NHEJ and knock-in oncogenes through HDR.