20.13 : Modelos Murinos para Estudo do Câncer

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.