1. Schematic overview of transplantation‐based mouse models and germline GEMMs
Schematic overview of transplantation‐based mouse models and germline GEMMs (A) Cancer cell line transplantation models are based on (orthotopic) inoculation of cultured human or mouse cancer cells in immunodeficient or syngeneic mice, respectively. (B) Patient‐derived tumor xenograft models or GEMM‐derived tumor allograft models are based on direct (orthotopic) implantation of human or mouse tumor fragments in immunodeficient or syngeneic mice, respectively. (C) In oncomice, de novo tumorigenesis is induced by transgenic expression of an oncogene (ONC) from a tissue‐specific promoter. (D) In tumor suppressor gene (TSG) knockout mice, de novo tumorigenesis is induced by germline inactivation of a TSG. (E, F) In conditional GEMMs, de novo formation of sporadic tumors is induced by tissue‐specific Cre‐loxP‐mediated inactivation of conditional TSG alleles (E) and/or activation of conditional oncogenes (F). Tissue‐specific expression of the Cre‐recombinase is achieved by crossbreeding with Cre transgenic mice, tamoxifen‐inducible Cre‐ERT transgenic mice, or by local administration of Cre‐encoding lenti‐ or adenoviruses. (G, H) Oncogene addiction can be studied using GEMMs with tamoxifen‐ or doxycycline‐inducible gene expression. (G) Administration of tamoxifen to transgenic mice carrying an oncogene‐ERT (ONC‐ERT) fusion will induce tumors that may undergo no, temporal, or durable regression upon tamoxifen withdrawal. (H) Similar studies can be performed by administration of doxycycline to bi‐transgenic mice with tissue‐specific expression of the reverse tetracycline‐controlled transactivator (rtTA) and carrying an oncogene or shRNA under transcriptional control of a tetracycline response element (TRE).
Kelly Kersten et al. EMBO Mol Med. 2016;emmm
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