Laboratory Mouse Genetics
The mouse is the best genetic model organism for human biology. Among the animals used in research, teaching and testing, mice comprise the majority of all experimental mammals. The animal is easy to house and to use. Moreover, mice produce family lines that express genetic traits or conditions that can mimic the human condition, both physiologically and genetically. This genetic similarity, combined with the great convenience of use, accounts for their popularity. Genetically defined mouse lines have proved crucial because they have allowed researchers all over the world to perform experiments on the same genetic material. This has allowed results to be directly compared.
Mice were first used in cancer research in 1894. Initially, mice were used for same-species tumor transplantations and drug treatment studies. The genetic utility of mice in human disease processes was first recognized early in the twentieth century, when William Ernest Castle and his students began an analysis of inheritance and genetic variation in mice. One of Castle's students, Clarence Cook Little, recognized the need for inbred genetically homogenous lines of mice. Little and his colleagues developed the most famous early inbred lines, including strains that were predisposed to develop tumors. Little also founded The Jackson Laboratory, located in Bar Harbor, Maine. This facility is now the world's foremost mammalian genetic research institution and the world's largest supplier of mice.
One of the early successes was the development of the famous mouse lines, BALB/c. These mouse lines were derived from albino mice. BALB/c mice have become a standard tool in hybridoma research.
In 1962, the discovery of a mutant mouse with low immunity, the nude mouse, led to human tumor transplantation. Its name refers to the gene locus nu/nu, and the mouse's lack body hair. A nude mouse fails to develop a thymus. The thymus controls the production of the immune system's T cells, lymphocytes that are essential to the immune system. Because of the absence of the thymus, nude mice suffer from a lack of cell-mediated immunity. Nude mice thus serve as a model system for the study of various cell mediated immune system behaviors. By transplanting an actual human tumor into a nude mouse, the tumor can be studied in a whole animal system.
In 1983, mice with severe combined immundeficiency (SCID) were discovered. SCID mice are more compromised with respect to immune system function than are nude mice. Tumors can be transplanted into SCID mice without being rejected. SCID mice have also proved to be a valuable biological factory for the production of antibodies that are necessary for many diagnostic, clinical ad experimental procedures.
A further breakthrough in the late 1980s led to transgenic mice, whose genes have been altered to produce a desired characteristic. Oncogenes, or genes that cause cancer, could then be studied in greater detail. Recombinant DNA technology facilitated the sequence comparison of the genomes of mice and humans. The genomes were shown to be very similar, with many functions controlled in a similar genetic fashion. As human genes for various targets were identified and cloned, the mouse homolog was often identified. The mouse could then be used for genetic, molecular, and biochemical studies that were relevant to a greater understanding of the functioning of the particular human gene. As well, transgenic mice were engineered, making possible the creation of mice to address specific questions and problems. For example, a specific trait, such as a predisposition to develop a particular type of tumor, could be introduced into a mouse strain. Such transgenic mice permit the study of cancer in specific tissues, including the initial stages of tumor development.
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