Overview

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.

The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research, including cancer research. A gene-of-interest can be added or deleted from a mouse’s genome using genetic engineering techniques, and if it causes tumor initiation in mice, it is highly likely to be a cancer-critical gene in humans. In addition, mouse models such as reporter mice can also be used to study the crucial stages of tumor initiation and their progression to aggressive cancers. In such mice, a reporter gene with luminescence or fluorescence tags is inserted into the cells under study to monitor their growth and proliferation.

Pre-clinical studies in mouse models serve as a perfect step between in vitro studies on cell cultures and clinical studies in humans. They can be used for investigating in vivo pharmacokinetics, toxicity, and anti-tumor efficacy of numerous chemotherapeutic agents before any of the drugs go to clinical trials. However, since mouse tumor cells or immune responses may not exactly represent the tumorigenic process in humans, mouse models have been developed that can closely mimic the tumor progression and immune responses in humans, for example, human tumor xenografts in immunocompromised mice or humanized mouse models.

In vivo testing in animals, including mice, can often raise ethical concerns. While it is true that experimentation in animals causes suffering, the benefits of animal experimentation in drug discovery are undeniable. Therefore, animal studies should be strictly avoided wherever alternative testing methods are available. In addition, experiments on animals should only be conducted after in vitro studies have been successfully performed on suitable cell lines.

Procedure

Mice and humans share various anatomical, cellular, and molecular characteristics. They also display approximately 80% orthology in their coding regions, making mice good model organisms for human cancer research.

Researchers can genetically engineer a mouse’s genome to mutate, delete, or over-express potential cancer-causing genes. Such transgenic mice are a valuable tool to study the effect of altered genes in tumor development and progression.

For example, a potential oncogene can be integrated into the mouse genome along with an appropriate promoter. If the over-expression of the gene leads to tumor development in the mouse, it indicates the oncogenic potential of the gene-of-interest.

Similarly, a knockout mouse that lacks a potential tumor suppressor gene can help researchers to understand the gene’s significance in tumor growth.

However, most tumor suppressor genes play an essential role in early mouse development. Therefore, a knockout mouse where a crucial tumor suppressor gene is silenced may not survive until adulthood.

In such instances conditional mouse models can be used. Here, a gene of interest is specifically inactivated only in targeted tissue cells or at a certain stage of development.

Mouse models called reporter models are engineered to co-express a gene with a fluorescent or luminescent reporter gene.

The reporter gene's simultaneous expression with a gene-of-interest, such as an oncogene, makes the cells luminesce. The researchers can then track any abnormal proliferation of the cells by monitoring cell luminescence. 

Mice also serve as important models for preclinical testing of new drugs against various cancers.

For example, in the xenograft mouse model, the human tumor cells are first transplanted into an immunocompromised mouse. Once the cells develop into an appropriately sized tumor, a drug is introduced into the mouse, and its effect on the cancer cells can be studied in vivo.

Although it is a very important research tool, the use of mice with compromised host immune systems does not truly represent the conditions inside an actual patient.

To overcome this problem, scientists have developed models called humanized mice, which have been altered to carry human genes, cells, or tissues to mimic a functional human immune system.