Apc KO Mice

Catalog Number: C001511

Strain Name: C57BL/6JCya-Apc^em2/Cya

Genetic Background: C57BL/6JCya

Reproduction: Heterozygote x WT

Strain Description

The adenomatous polyposis coli (APC) gene is a tumor suppressor gene, the protein it encodes plays a key regulatory role in the Wnt/β-catenin signaling pathway ^[1]. The APC protein can antagonize the Wnt signaling pathway, assisting in regulating cell migration, adhesion, transcriptional activation, and apoptosis. More than 10% of human tumors have mutations in the APC gene, and most colorectal cancers have mutations in the APC gene ^[2]. Defects in the APC gene lead to the occurrence of familial adenomatous polyposis (FAP), characterized by hundreds to thousands of adenomatous polyps in the rectum. This is an autosomal dominant precancerous disease, which usually develops into malignant tumors ^[1-2]. Disease-related mutations in the APC gene are highly prevalent in a small region known as the mutation cluster region (MCR), which usually leads to the production of truncated proteins ^[3-4]. In mice, either Apc gene deletion or multiple intestinal neoplasia (Min) mutations that result in the production of truncated APC proteins cause phenotypes similar to human familial adenomatous polyposis (FAP) and/or colorectal tumors ^[5-9].

The Apc KO mouse is a research model constructed by using gene editing technology to knock out the sequence in the mouse Apc gene that contains the mutation cluster region (MCR), and this strain is homozygous lethal. Heterozygous Apc KO mice can spontaneously develop intestinal adenomas and exhibit significant colorectal cancer disease phenotypes in various aspects such as survival, growth, food intake, and intestinal lesions. Therefore, Apc KO mice can be used for familial adenomatous polyposis (FAP) and colorectal cancer and other tumors or tumor-related diseases, as well as the study of the regulatory mechanism of the Wnt/β-catenin signaling pathway.

Strain Strategy

The Apc gene is located on chromosome 18 in mice and contains a total of 16 exons. Gene editing technology is used to knock out a portion of the 16th exon of this gene. This exon occupies more than 70% of the coding region of the Apc gene and includes the mutation cluster region (MCR) corresponding to high-frequency mutations in human diseases.

Applications

• Research on the regulatory mechanism of the Wnt/β-catenin signaling pathway;
• Research on familial adenomatous polyposis (FAP);
• Research on colorectal cancer;
• Research on other APC-related tumors.

Validation Data

1. Survival curve

Figure 1. Survival curves of Apc KO mice and wild-type mice (WT)*. The data shows that compared to male mice, female Apc KO mice die earlier. Female Apc KO mice start to die in the 20th week, and the mortality rate reaches 50% at 27 weeks, while male Apc KO mice start to die in the 26th week, and the mortality rate reaches 50% at 34 weeks (n=10).

*Note: Due to the lethality of the homozygous strain, the Apc KO mice referred to in this manual are all heterozygous Apc knockout mice (Apc^+/-), and all data are obtained under normal dietary conditions.

2. Growth Curve

Figure 2. Growth curve of Apc KO mice and wild-type mice (WT). The data shows that compared to the wild-type control group, both female and male Apc KO mice have reduced body weight (n=10).

3. Food Intake

Figure 3. Comparison of food intake between Apc KO mice and wild-type mice (WT). The data shows that compared to the wild-type control group, both female and male Apc KO mice have reduced food intake (n=10).

4. Intestinal Anatomy

Figure 4. Observations of the intestinal tissue anatomy of Apc KO mice and wild-type mice (WT). The results show that Apc KO mice can spontaneously form intestinal adenomas. At the age of 9 weeks, most Apc KO mice have developed adenomas in the intestines, and the adenomas are mostly located in the small intestine, especially in the ileum (the same as the high incidence of tumors in the classic Apcmin mouse model ^[10]). In addition, some Apc KO mice also develop adenomas in the large intestine (the data shown are representative images after the dissection of the mouse intestine).

5. Morbidity and Number of Adenomas

Figure 5. Statistics on the morbidity and number of intestinal adenomas in Apc KO mice. The onset of disease in Apc KO mice is confirmed by observation records, including symptoms such as whitening of the nails, bloody stools, prolapse, or abdominal swelling in the mice. The results show that at the age of 18~19 weeks, about 50% of the mice show more obvious external manifestations, which can be confirmed as the occurrence of intestinal adenomas, and all mice are sick around the age of 25 weeks. The statistics on the number of intestinal adenomas show that Apc KO mice can spontaneously form intestinal adenomas at the age of 9 weeks, and with time, the number of intestinal adenomas in mice gradually increases. Due to individual differences, the number of adenomas formed in different mice varies.

6. Intestinal Tissue Pathology

Figure 6. H&E staining detection of intestinal tissue from wild-type (WT) mice and Apc KO mice of different ages. The results show that adenomas have already formed in Apc KO mice at the age of 9 weeks, and the volume of the adenomas increases over time.

Summary

Apc KO mice exhibit significant colorectal cancer disease phenotypes in terms of survival, growth, food intake, and intestinal lesions. The survival time of female heterozygous Apc KO mice is shorter, with a mortality rate reaching 50% at 27 weeks, while males reach this proportion at 34 weeks. In terms of body weight and food intake, both female and male heterozygous Apc KO mice are lower than wild-type mice. In terms of intestinal lesions, Apc KO mice can spontaneously form intestinal adenomas under normal dietary conditions, and the number increases over time, mainly distributed in the small intestine, especially the ileum, and some mice also have adenomas in the large intestine. Therefore, Apc KO mice can be used to study the pathogenesis of familial adenomatous polyposis (FAP) and colorectal cancer, develop and test the long-term efficacy of new treatment strategies, and study the regulatory mechanism of the Wnt/β-catenin signaling pathway and other APC-related tumors. 

Precautions

Due to individual differences and environmental factors, the actual incidence of this model may vary. The data in this manual is obtained under the conditions of Cyagen's internal facilities and is for reference only. The specific disease situation of mice should be based on the actual situation, please use it appropriately according to the actual situation.

References
[1]Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci. 2007 Oct 1;120(Pt 19):3327-35.
[2]My Cancer Genome. (2024). APC. Retrieved May 7, 2024, from https://www.mycancergenome.org/content/gene/APC/
[3]Näthke I. APC at a glance. J Cell Sci. 2004 Oct 1;117(Pt 21):4873-5.
[4]Kohler EM, Derungs A, Daum G, Behrens J, Schneikert J. Functional definition of the mutation cluster region of adenomatous polyposis coli in colorectal tumours. Hum Mol Genet. 2008 Jul 1;17(13):1978-87.
[5]Moser AR, Luongo C, Gould KA, McNeley MK, Shoemaker AR, Dove WF. ApcMin: a mouse model for intestinal and mammary tumorigenesis. Eur J Cancer. 1995 Jul-Aug;31A(7-8):1061-4.
[6]Ren J, Sui H, Fang F, Li Q, Li B. The application of ApcMin/+ mouse model in colorectal tumor researches. J Cancer Res Clin Oncol. 2019 May;145(5):1111-1122.
[7]Cheung AF, Carter AM, Kostova KK, Woodruff JF, Crowley D, Bronson RT, Haigis KM, Jacks T. Complete deletion of Apc results in severe polyposis in mice. Oncogene. 2010 Mar 25;29(12):1857-64.
[8]McCart AE, Vickaryous NK, Silver A. Apc mice: models, modifiers and mutants. Pathol Res Pract. 2008;204(7):479-90.
[9]Washington, K., Zemper, A.E.D. Apc-related models of intestinal neoplasia: a brief review for pathologists. Surg Exp Pathol 2, 11 (2019).
[10]Yamada Y, Mori H. Multistep carcinogenesis of the colon in Apc(Min/+) mouse. Cancer Sci. 2007 Jan;98(1):6-10.