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Genotype, Environment, Gene Environment Interaction, Special Populations, Molecular Genetics

Rodents are members of the order Rodentia, a large group of biologically similar animals that includes rats, mice, and beavers. Two of these species, rats and mice, are the most commonly used animal models for aging research.

Many types of aging research cannot be conducted with human subjects. In situations where the research requires a living organism, and humans are not suitable, investigators must search for a suitable animal model. Humans may not be suitable because they choose their mates, and thus genetic control is not possible; because they live freely, rather than in controlled environments; because the research may result in unacceptable risks of pain, emotional distress, or illness; or because the research requires observing the subjects for a lifetime and humans live too long.

The range of animal models used in aging research is very wide and includes very small nematode worms (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), rats, mice, dogs, monkeys, and chimpanzees. Of all of these models, rats and mice are the most commonly used because they have reasonable lifespans (two to four years), they are mammals and therefore share a great many genes with humans, and because a very great deal is known about their physiology, behavior, and genetic makeup. Thousands of mice and rats are specially bred each year throughout the world for biological, biomedical, and behavioral research. Much of what is learned is published in the scientific literature and available to scientists virtually anywhere on earth. The publication of research results in this way allows the sharing of information, reducing the amount of duplication of research. Information sharing also makes each piece of research more meaningful than it might otherwise be, since each investigator can place his or her research in the context of what else is known about that species.

While rats and mice are not as similar to humans as are nonhuman primates (monkeys and chimps), they have the advantages of small size and relatively easy husbandry, and they share many genes with all mammals including humans. Nonhuman primates are very much like humans, sharing perhaps 95 percent of their genes with humans. They are therefore the model of choice for some sorts of research, especially research that requires large brains, complex behavior, and long life spans. Chimps, for example, live up to seventy-five years, are capable of very complex behaviors and emotions, and probably develop late life diseases like Alzheimer’s disease that seem to require years to develop. Because they are large, complex animals with long life spans they are very expensive to maintain. They also cannot be used in many of the same types of research where humans cannot be used.

The use of animal models for research is controversial. Special attention is paid to nonhuman primate research. Use of all animals is carefully monitored, housing requirements are justifiably strict, and social needs are regulated. The large size and complex behavior of nonhuman primates makes these animals especially expensive to maintain and study.

Since rats and mice are relatively easy to maintain, relatively economical, and large numbers can be bred and maintained in relatively small vivaria, they have been the models of choice for decades. Many of the mouse strains currently used for research are descendants of mice bred by European zoologists in the nineteenth century. These zoologists bred their mice for specific characteristics, such as coat color, and began analysis of the genetic control of such characteristics. In the early part of the twentieth century biologists began to breed mice, and to a lesser extent rats, for susceptibility to diseases, especially cancer. Rats were used where a larger body size or blood volume were needed for research, mice where small body size and smaller fluid volumes were acceptable. Mice, being smaller, were cheaper, and somehow seemed more attractive—or less objectionable—as well. In research programs throughout the twentieth century, rats have been most used for physiological research because of their large size, and mice in genetic research because of their small size. Use of mice and rats continues to follow this general pattern although micro-methods have made mice more available for physiological research and the collection of more genetic information about rats has made them more available to geneticists.

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