TABLE 2.
Murine models of CRC.
| Model | Strategy for model generation | Pathological mechanism | Detailed methodology | Range of application | Limitations | References |
|---|---|---|---|---|---|---|
| Spontaneous animal model of CRC | Mutant animal models of CRC | Proliferation | Mutation in APC | FAP model for studying hereditary CRC | Survival time < 4 months, tumor formation in small intestine, difficulty in metastasis | Moser et al. (1990) |
| Shoemaker et al. (1997) | ||||||
| Shoemaker et al. (1998) | ||||||
| Barker et al. (2007) | ||||||
| Mutation in APC/Cre | Induction of colorectal adenoma | Difficulty in metastasis | Robanus-Maandag et al. (2010) | |||
| Chen et al. (2020) | ||||||
| Mutations in Mlh1, Msh2, Msh3, Msh6, and Pms2 | Hereditary nonpolyposis CRC (HNPCC) | Multi-tissue tumors, difficulty in metastasis | Lynch et al. (1997) | |||
| Papadopoulos and Lindblom (1997) | ||||||
| Manceau et al. (2011) | ||||||
| Mutation in SMAD4 | Familial juvenile polyposis model, acceleration of tumor development | Difficulty in metastasis | Takaku et al. (1998) | |||
| Lu et al. (1998) | ||||||
| Mutation in KRAS | Induction of colonic hyperplasia and generation of aberrant crypt foci (ACF) carcinogenesis model | CRC cannot be induced by mutations in single genes, but is induced in combination with other gene mutations that induce carcinogenesis and enhance the incidence of CRC. | Bos et al. (1987) | |||
| Campbell et al. (1998) | ||||||
| Jen et al. (1994) | ||||||
| Janssen et al. (2002) | ||||||
| Janssen et al. (2006) | ||||||
| Calcagno et al. (2008) | ||||||
| Mutation in PIK3CA | Induction of colon adenoma | Single mutations generally do not induce CRC. | Juric et al. (2018) | |||
| Invasion and metastasis | Mutation in FBXW7 | Model of highly invasive colorectal cancer | Single mutations generally do not induce CRC. | Mao et al. (2004) | ||
| Mutation in p53 | Induction of distal intestinal tumor | Single mutations generally do not induce CRC. | Nakayama et al. (2017) | |||
| Kadosh et al. (2020) | ||||||
| Diet- and chemical-induced models of CRC | Diet-induced models of CRC | Inflammation | High-fat diet (HFD)/western diet (NMD) | Colorectal barrier dysfunction and inflammation, invasive adenocarcinoma | Requires a long duration and has a low carcinogenic efficiency | Itano et al. (2012) |
| Yu et al. (2022) | ||||||
| Chemical-induced models of CRC | 2,4,6-Trinitro-benzenesulfonic acid (TNBS) | Induction of colitis-driven CRC | Cannot be used alone, necessary to break the intestinal mucosal screen before use, mortality rate of modeling is high | Scheiffele and Fuss (2002) | ||
| Anaerobic oxidation of methane (AOM) + dextran sodium sulfate (DSS) | Tumors driven by colitis, induced distal CRC | The modeling rate is low and molding time is uncertain | Neufert et al. (2007) | |||
| De-Robertis et al. (2011) | ||||||
| Liang et al. (2017) | ||||||
| Sun et al. (2022) | ||||||
| Proliferation | AOM | ACF and CRC epithelial tumor model | The period of modeling is long and time-consuming, cannot be used for studying CRC metastases | Femia and Caderni (2008) | ||
| Izzo et al. (2008) | ||||||
| Orlando et al. (2008) | ||||||
| 1,2 Dimethyl hydrazine (DMH) | Human sporadic CRC research model, tumorigenicity specificity | Requires a long time and has a low carcinogenic efficiency | Ma et al. (1996) | |||
| Kissow et al. (2012) | ||||||
| Aranganathan and Nalini (2013) | ||||||
| Parahydrogen-induced polarization (PhIP) | ACF-induced rat model | Low incidence, long study cycle | Ito et al. (1991) | |||
| Tanaka et al. (2005) | ||||||
| 3,2′-Dimethyl-4-Aminobiphenyl (DMAB) | Induced colon and small intestinal carcinogenesis | Requires multiple administration, low specificity | Reddy and Mori (1981) | |||
| Reddy (1998) | ||||||
| CIN | N-ethyl-N-nitrosourea (ENU)/N- methyl -N-nitrosourea (MNU)/N-methyl-N-nitrosoguanidine (MNNG) | Induced distal CRC model | Induced mutations are random and drug volume quantification is difficult | Huang et al. (2020) | ||
| Animal model of transplanted CRC | Animal model of orthotopic tumor transplantation | Invasion and metastasis | Cecal transplantation | Induction of primary CRC that can metastasize to local lymphatic vessels, lungs, and liver | Risk of laparotomy is high in this model. CRC originates from the mucosa, and whether tumor metastasis results from the overflow of intraperitoneal cells cannot be excluded | Talmadge et al. (2007) |
| Martin et al. (2013) | ||||||
| Lee et al. (2014) | ||||||
| O'Rourke et al. (2017) | ||||||
| Animal model of ectopic tumor transplantation | Spleen planting | Study of advanced CRC | The operation is complex and requires highly advanced technical skills | Kasuya et al. (2005) | ||
| Bai et al. (2015) | ||||||
| Yang et al. (2021c) | ||||||
| Tail vein injection | Lung metastasis model of CRC | Differs from human CRC metastasis, multiple metastases are prone to occur | Wang et al. (2020) | |||
| Liver implantation | Liver metastasis model of CRC | Only the late metastatic process of CRC is simulated; tumor forms only at the site of implantation | Panis and Nordlinger (1991) | |||
| Kopetz et al. (2009) | ||||||
| Roque et al. (2019) | ||||||
| Intraperitoneal injection of CRC cell for inducing metastasis | Peritoneal metastasis model of CRC | Unsuitable for studying early metastasis of lymph nodes in CRC. | Li et al. (2016) | |||
| Proliferation | Hypodermic implantation | Real-time monitoring of CRC growth | Cannot simulate the in situ growth of CRC, not easy to study tumor invasion and metastasis | Rygaard and poulsen (1969) | ||
| Lehmann et al. (2017) |