Read this article to learn about the various applications of transgenic mice.
Mouse, although not close to humans in its biology, has been and continues to be the most exploited animal model in trans-genesis experiments.
The common feature between man and mouse is that both are mammals. Transgenic mice are extensively used as animal models for understanding human diseases and for the production of therapeutic agents. Adequate care, however, must be exercised before extrapolating data of transgenic mice to humans.
Mouse models for several human diseases (cancers, muscular dystrophy, arthritis, Alzheimer’s disease, hypertension, allergy, coronary heart disease, endocrine diseases, neurodegenerative disorders etc.) have been developed. A selected few of them are briefly discussed.
1. The Human Mouse:
The transgenic mice with human immune system were produced, and they are commonly referred to as human mice (Fig. 41.5). For this purpose, mice with severe combined immunodeficiency (SCID-a condition characterized by total lack of immune system cells) were chosen.
Human thymus tissue from an aborted fetus was transplanted under the capsule membrane of the kidney of the mouse. Human lymph node was placed under the opposite kidney. After about a week, immature immune cells (T-lymphocytes) from a human fetus were injected into the mouse tail vein.
These lymphocytes enter the thymus tissue under the kidney and mature to T-lymphocytes. The so produced T-lymphocytes enter the circulation and in the lymph node (present under the second kidney), they multiply to form a full-pledged functional immune system. It takes about two weeks after the transplant for the mice to display the human immune system (characteristics of both T-lymphocytes and B-lymphocytes).
The human mouse, being a close animal model for human immune system is a boon for immunologists, particularly working on AIDS. This is because the various immunological aspects of AIDS including the possible development of an AIDS vaccine can be explored by using human mouse (Note: There is no good animal model for AIDS research except chimpanzee).
2. The Alzheimer’s Mouse:
Alzheimer’s disease affects about 1% of the population between 60-65 years old, and about 30% of the population over 80 years old. This disease is characterized by progressive loss of memory and personality changes (decline in thinking, judgment etc.). The postmortem analysis of brains of Alzheimer’s patients revealed plaques of dead nerve cells entangled in a protein called amyloid.
This protein was purified and its amino acid sequence determined. Later, amyloid precursor protein (APP) and its gene sequence were also identified. Alzheimer’s disease is more prevalent in some families, clearly indicating a genetic basis for this disease.
Transgenic mice were developed by introducing amyloid precursor gene into fertilized egg cells of mice. The synthesis of human amyloid protein and its accumulation as typical plaques in the mice brain were observed. The Alzheimer’s mouse is very useful in understanding the pathological basis of the disease. Certain mutations in APP gene and the involvement of some other genes are believed to be responsible for Alzheimer’s disease.
3. The Oncomouse:
The animal model for cancer is the oncomouse (onco refers to cancer). First developed for breast cancer, the oncomouse is useful for understanding of cancer and evolving modalities for cancer therapy. The oncogene c-myc in association with mouse mammary tumor (MMT) virus was found to be responsible for breast cancer in animals. Transgenic mice were produced by introducing chimeric DNA consisting of c-myc gene and sections MMT virus into fertilized mouse egg cells.
Breast cancer developed in adult female mice and the trait was passed on to the offspring. Oncomouse (the mouse that is genetically altered and is susceptible for cancer) was patented by U.S. Patent office in 1988. In fact, it was the very first animal to be patented.
4. The Prostate Mouse:
The prostate gland, surrounding the urethra of males is responsible for secreting semen fluid. In the older men, particularly above 60 years of age, prostate gland gets enlarged and may become cancerous. The oncogene for prostate cancer was identified (int-2). A chimeric DNA by joining int-2 with viral promoter was prepared and introduced into fertilized mouse eggs. In the transgenic mice so developed, enlargement of prostate gland was observed. There prostate mice were also patented in 1991.
5. The Knockout Mouse:
The basic principles underlying gene knockout have been described .Several knockout mice have been developed. It is not an exaggeration that the knockout mice have become as common as a test tube in the laboratory for a biotechnologist. It must be noted that not all the knockout mice are immediately useful for human health and welfare. A selected few of the knockout mice are described.
SCID mouse:
Severe combined immunodeficiency (SCID) is a condition with a total lack of immune system. SCID mice were developed by eliminating a single gene and the resultant mice lost the ability to produce B-lymphocytes and T-lymphocytes. The human mouse was later developed from the SCID mouse.
Knockout mouse for allergy:
The receptor sites on certain body cells for IgE antibodies are believed to be responsible for triggering allergy reactions. Knockout mice were developed for allergy by removing the gene encoding for receptor protein. The result is that antibodies cannot bind to cells due to lack of receptors and the mice are unaffected by allergic reactions. It is expected that some breakthrough may occur in the near future to benefit the millions of sufferers of allergic reactions, spread throughout the world.
Knockout mouse for transplantation:
By using a suicide gene, the liver cells were destroyed in a mouse that already lacks immune system. Sample human liver cells were transplanted in this mouse. Encouraged by lack of immune system, the human liver cells can develop. In this fashion, organ replacement in animals is possible.
Knockout mouse with memory loss:
The memory processes in brain are believed to be carried out by a specialized area called hippocampus. By a gene knockout technique, researchers have developed mice that lack hippocampus. These knockout mice lacked the ability to remember.
Knockout mouse with retinitis pigmentosa:
By inactivating the mouse rhodopsin gene, rods cells of the retinal deteriorate in the transgenic mice. This retinal degeneration is comparable to human retinitis pigmentosa. The rhodopsin knockout mouse is useful for understanding the retinal degeneration, besides evolving therapeutic strategies.
6. Transgenic Mice for Human Diseases:
Transgenic mice are important for the development of therapeutic drugs and possible gene therapies, besides the understanding of the human disease. Many transgenic mice with human disease equivalents have been developed and a selected few of them are given in Table 41.1.
