. 2015 Jun 26;37(8):909–920. doi: 10.1002/bies.201500032

Table 3.

Selection of genetically modified mouse models of colorectal cancer

Mouse allele	Rationale	Strategy	Advantages	Disadvantages
Apc^Min/+ 47, 48	• N/A	• Germline truncating mutation (N terminus)	• Model of human familial adenomatous polyposis (FAP) syndrome and >80% of sporadic CRCs contain mutations 2, 4	• Developed hundreds of low‐grade adenomas
Apc^Min/+ 47, 48	• Ethylnitrosurea (ENU) mutagenesis screen	• Loss of heterozygosity occurs at wildtype allele in tumours	• Short‐lived for rapid studies	• Short‐lived as tumour burden causes obstruction, prolapse and bleeding
	• Ethylnitrosurea (ENU) mutagenesis screen		• Tumour multiplicity easily quantifiable	• Short life‐span means that adenomas do not acquire sufficient mutations to progress to adenocarcinoma and metastasise 56, 57
				• Tumours predominantly located in small rather than large intestine
Msh2^−/− 54	• Msh2 mutations common in CRC	• Germline knock‐out	• Model of Hereditary non‐polyposis CRC (HNPCC) or Lynch Syndrome (3% of all CRCs)	• Msh2 mutation in all cells of body and mice are predisposed to lymphomas
Villin‐Cre/Msh2^LoxP 55	• To restrict malignancy to intestine to prevent lymphoma	• Conditional	• Developed intestinal adenomas and adenocarcinomas	• Do not develop metastases
Villin‐Cre/Msh2^LoxP 55	• To restrict malignancy to intestine to prevent lymphoma	• Cre recombinase ^a expressed from promoter of intestinal specific gene (Villin)	• No deaths from lymphoma
Apc^580S/580S 64	• To model advanced CRC by restricting tumours to colon and reducing tumour burden	• Conditional Adenoviral Cre recombinase ^a is administered through the anus to inactivate Apc	• Live >1 year.	• Do not develop metastases
			• Developed two or three intestinal adenomas	• Conditional allele (unactivated) reduces Apc expression in all cells, similar to Apc^fl/fl 10, which results in development of life‐limiting hepatocellular carcinomas by 14 months (REM unpublished observations of Apc^580S/580S)
			• Some mice developed adenocarcinomas
Apc^lox15/+; Fabpl‐Cre 109	• To model advanced CRC by restricting tumours to the colon and reducing tumour burden	• Conditional	• Live >1 year.	• Do not develop metastases
		• Cre‐recombinase ^a is expressed in the distal small intestinal and colonic epithelia to inactivate Apc	• Developed two or three intestinal adenomas	• Do not develop metastases
			• Some mice developed adenocarcinomas
Apc^Min/+Trp53^−/− 110	• To model advanced CRC through addition of cooperating gene mutations	• Germline mutations in Apc and Trp53		• Do not develop metastases
Apc^2lox14/+ KrasLSL‐G12D and Fabpl‐Cre 111	• To model advanced CRC through addition of cooperating gene mutations	• Conditional	• Developed more adenocarcinomas than single mutant (Apc or Kras alone) control mice	• Do not develop metastases
Apc^2lox14/+ KrasLSL‐G12D and Fabpl‐Cre 111		• Cre‐recombinase ^a is expressed in the distal small intestine/colonic epithelia and results in constitutive activation of K‐Ras and inactivation of Apc		• Do not develop metastases
Apc mutant with disruption of Tgfbr2, Smad2 or Smad4. 112, 113, 114	• To model advanced CRC through addition of cooperating gene mutations		• Developed more adenocarcinomas than single mutant control mice.	• Do not develop metastases
Apc^Min/+ Villin Cre Fbxw7^(ΔG) 115	• To model advanced CRC through addition of cooperating gene mutations	• Germline mutation of Apc	• Decreased lifespan	• Do not develop adenocarcinomas or metastases
		• Conditional mutation of Fbxw7	• Increased tumour burden
		• Cre recombinase ^a expressed from promoter of intestinal specific gene (Villin)	• Fbxw7 null control mice developed adenomas by 9‐10 months of age
Apc^CKO/CKO‐LSL‐G12D; Kras^tm4tyj/+ 62	• To model advanced CRC through addition of cooperating mutations. To restrict tumours to the colon and reduce tumour burden	• Adenoviral Cre solution administered via the anus to simultaneously disrupt Apc and activate K‐ras	• Developed adenocarcinomas after five months	• Labour intensive mouse surgery required to clamp a section of colon to deliver Adenoviral Cre solution to the colon via the anus
			• Developed metastases to distant organs after six months e.g. liver
			• In vivo monitoring via colonoscopy

CRC, Colorectal carcinoma.

^{^a}

Cre recombinases catalyse recombination between two loxP sites that are situated in the introns surrounding a critical exon(s) and result in excision of the DNA between the sites.