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    Mighty mice
    Solving the mystery of disease with transgenic techniques

    The mouse, small enough to fit in your hand, is making large contributions to medical research. By inserting DNA into the nuclei of single-cell fertilized mouse eggs, scientists are breeding mice that develop human-like conditions - mice that get Alzheimer's disease or mice that show signs of asthma. The study of such "animal models" of human disease may lead to advances in medical therapy, so that even such diseases as cancer or AIDS may one day be prevented or cured. Manipulating the genetic material of a laboratory animal is part of a field of study called transgenic research - and it's helping scientists understand the role of genetics in human disease.
    Transgenic research is rooted in genetics

    Your body contains some 60 trillion cells. The material that controls the growth and activities of cells is contained in the genes. Within the nucleus of each of your cells reside 46 chromosomes - half from your mother and half from your father. Chromosomes contain twisted, double strands of deoxyribonucleic acid (DNA). You might think of DNA as a twisted ladder. Your genes are specific portions of that "ladder."

    Throughout your life, your genes tell your cells what proteins they need to make to help keep you healthy. If a gene is missing, incomplete, damaged or duplicated, this process is altered, which may lead to disease.

    Each of your cells contains approximately 100,000 genes (the human genome). A single abnormal gene may increase your risk of becoming ill. A combination of altered genes and certain external factors (such as diet, whether you smoke) can further increase your risk of becoming ill.

    By pinpointing or "mapping" the location, on the chromosome, of each gene in the human body, and understanding the gene's function, scientists hope to discover new ways to approach the prediction, prevention, diagnosis and treatment of disease. They hope to answer why one member of a family gets an illness, and another doesn't. Transgenic research can play a major role in understanding gene function.

    How transgenic research works

    From family studies and genetic testing, researchers can determine if a particular gene seems to be implicated in a particular disease. To test the hypothesis, scientists first "isolate" the suspect human gene. Then they microinject fragments of DNA containing the suspect human gene (or in some cases a copy of that gene from another species) into the nucleus of a one-celled fertilized mouse egg.

    Once inside the nucleus, there is a 1 percent to 5 percent chance that the transferred gene will become integrated as part of the mouse chromosome. If integrated, the transferred gene is then a part of the animal genome and is transmitted generation after generation.

    To ensure that every cell in a fully developed mouse contains the transferred gene, the microinjection must occur at the single-cell stage of mouse development - before cell division and differentiation have begun. The timing has to be perfect.

    Once injected, the mouse embryos are then implanted in the uterus of an adult female mouse (a surrogate mother). After birth, the mice are screened to check whether they carry the integrated gene (now called a "transgene"). As adults, these transgenic mice will be bred with nontransgenic mice of the same breed, so that half of the offspring will contain the transgene and half will not. This ensures that with each generation of mice bred, there is always a "control" group with which to compare the genetically engineered mice.

    Mice are widely used in transgenic research because their genetic makeup closely resembles that of humans, because it is easy to manipulate mice embryos, and because mice reproduce quickly. Pigs and cows are sometimes used in transgenic research, and transgenic research does not have to involve human DNA; it can involve transferring genetic material of one animal to another of the same or different breed.



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