2.6 Genetically Engineered Mouse Models (GEMs)
Cancer in genetically altered animals is more similar to human cancer than the other models because the tumour develops naturally in its original site, as opposed to xenograft tumours, which are frequently implanted in areas other than an orthotropic site. The tumours have the same natural growth rate and metastatic characteristics as seen in humans. The immune compromised animal is not required to grow these tumours because they are non-immunogenic in their natural host(Navale, 2013).
The GEMs are classified into two types: transgenic mice and knockout mice.
2.6.1 Transgenic Mice: A foreign gene is injected into the pronucleus of a fertilised egg to create the transgenic mouse. This off spring then harbours and expresses the foreign gene, carrying it down the line. Genes can enter the pronucleus through microinjection, retroviral infection, and embryonal stem cell (ESC) transfer. Transgenic animals make excellent models for studying the oncogenic phenotype brought on by the dysregulation of a known gene.
Oncogene-expressing transgenic mice, which spontaneously develop tumours as a result of a known biochemical pathway defect, are excellent models for testing medications that target a specific biochemical pathway. Examples include the c-fos, N-myc, and NF1 genes in neurofibromatosis, as well as the erb B2 gene in transgenic mice. For example, Ras inactivation has been linked to the emergence of several cancers, including breast cancer. Researchers evaluated the effectiveness of new chemotherapy regimens designed specifically for treating breast cancer in transgenic mice with rat mutations that cause mammary tumours(Navale, 2013).
2.6.1.1 TRAMP transgenic mice: The expression of SV40 tumour antigens is controlled by a modest probasin promoter. Within 12 weeks of birth, these mice acquire prostate cancer, which progresses to metastases by 30 weeks. Many important characteristics of human prostate cancer are replicated in TRAMP mice(Abate-Shen and Shen, 2002).
2.6.1.2 p53+/- Wnt-1transgenic mice: To generate the model of mammary carcinogenesis, p53+/-mice were crossed with MMTV-Wnt-1 transgenic mice. MMTV stands for mouse mammary tumour virus promoter(Hursting et al., 2005).
2.6.1.3 Apc deficient mice: A dominant mutation in theApc (adenomatous polyposis coli) gene causes these mice to spontaneously grow preneoplastic intestinal polyps. Most human colon tumours have this gene mutated(Hursting et al., 2005).