Rodents
RODENTS
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.
Genotype
Among the tremendous advantages that recommend rodents for research, the ability to control genetic and environmental variables are the most significant. By rearing the animals in controlled environments, it is possible to almost completely eliminate the risks of infectious diseases. This is accomplished by placing the animals in facilities called barrier facilities. These facilities have no windows, which allows control of the exposure to light; the animal rooms are sealed and air entering the rooms is filtered to exclude airborne sources of infection or irritation; food bedding cages and water are sterilized; and caretakers take complete showers before entering these rooms. These precautions reduce the possibility that changes observed with advancing age are due to disease. This makes it more likely that changes are the result of ‘‘normal aging.’’ The development of such barrier facilities led to a doubling of the observed life span of rats and mice over the twenty years from 1970 to 1990. Much of what was once thought to be the inevitable consequence of aging appears to be the consequence of disease. This evolution in health and life span of laboratory animals with improvements in husbandry is reminiscent of the similar changes in human health and life span with the development of improved public health and the advent of antibiotics during the twentieth century.
Environment
Environmental control has another very important function. By producing controlled environments that differ in some single variable (e.g., temperature) it is possible to isolate that variable and determine its effects upon the health, behavior, or longevity of the animals being studied. Variables that can be tested in this way range from simple aspects of the environment such as day length, temperature, and humidity to more complex variables such as feeding regimen and nutrition, drug dose or route of administration, or social interaction with cage mates.
The power of environmental control in these rodent models (and in some lower species such as fruit flies as well) is greatly increased by the genetic control that can be applied at the same time. By a process of inbreeding (mating to close relatives) mice and rats can be made to share all or most of their genes. Inbred strains are the most commonly used examples of such control. Inbred strains are the result of at least twenty generations of brother-sister mating. After twenty generations new mutations are adding genetic diversity, in the form of new genes at the same rate that gene differences are being eliminated by the inbreeding process. However, at this point the differences between the animals within the inbred strain are very slight. The animals are as genetically identical as are identical twins. Thus, it is possible to produce large numbers of genetically identical mice or rats, all the same age and at the same time.
Gene environment interaction
By studying genetically controlled rodents in controlled environments, it is possible to discover whether a phenomenon is determined by genes, the environment, or both. For example, assume an investigator wanted to discover whether genetic differences or exposure to some environmental factor causes cataracts in mice. In this example, the investigator suspects that the cause is bright light, but he has also noticed that not all of his animals get cataracts. To further complicate matters, the animals that do get cataracts get them at different ages. To test whether environmental factors affect cataract formation, this investigator can place genetically identical mice in different parts of the animal room, near to lights and further away from lights. Differences in number of cataracts formed and the age at which they are formed must be due to environmental differences, since the animals are genetically identical. In this case, he will find that animals on the top of the cage rack will develop more cataracts sooner than animals further from the ceiling lights in the room. To determine whether genes affect cataract formation the investigator can place mice of different strains in the same environment. By putting mice of more than one strain close to the lights he will find that mice of some strains are more susceptible to cataract formation than are others. Thus, he will have shown that both the environment and genes are important in the development of cataracts.
While many, perhaps most, variables are affected by gene-environment interaction, the relative contributions of genes and environment differs from one variable to another. Eye color is largely determined by genes. Skin wrinkling is largely determined by exposure to sunlight (U.V. light). One of the objectives of research is to find the genetic and environmental factors that underlie age changes and age-related diseases in order to be able to improve the health of individuals and allow them to reach their maximum potential life span.
The genotype of the individual (or inbred strain) is the total set of genes that animal carries. The phenotype of the individual is the set of characteristics that the animal manifests, and is the result of the genotype and its interaction with the environment in which it is expressed. Most such interactions are complex and not as simple as hair color or eye color. Genes interact with one another and with environmental variables. Single traits, such as height or body weight, may be the result of several genes and their interaction with nutritional variables, activity level, and room temperature. Very complex traits, such as depression, anxiety, emotionality, intelligence, and longevity, are undoubtedly the result of the interactions of many, many genes and many environmental factors as well.
Special populations
A variety of special genetic populations of rodents have been developed in order to try to conduct analyses of these complex interactions. These include hybrid populations that carry genes from more than one parental type in predictable proportions, congenic lines that are genetically identical except for differences in a single gene of interest, and genetically selected lines that have been selected for a single trait such as long life, absence of cancer, or high activity rate. Selected populations offer a chance to find sets of genes that influence a trait such as longevity. In the selection process, mice (or rats or nematodes or fruit flies) are mated and then the life spans of the offspring are observed. The longest-lived are mated to one another and so on for many generations. The result is a population of mice with increased longevity. The genetic differences between these animals and their shorter-lived progenitors can then be studied for clues to fundamental aging processes. These genetic factors are likely to be complex and multifactorial. Some genes may be parts of large arrays of genes all of which contribute a small amount to the final expression of a trait. Traits of this type are referred to as quantitative traits. New methods of analysis, such as quantitative trait locus (QTL) analysis, are being developed to cope with this complexity.
Molecular genetics
A major area of rodent model development that has resulted from the revolution brought to biology by molecular genetics is the creation of mice that are lacking a specific gene (called knock outs ) or that have extra copies of such a gene (called knock ins ). By deleting or adding genes it is possible to observe the effects of that gene very specifically. While the results of these manipulations have not always been as clear-cut as expected, this research approach offers a significant increase in the precision of genetic manipulation. These and other genetic manipulations result in what are commonly called designer mice and rats and as such represent the cutting edge of current animal model development.
Richard L. Sprott
See also Genetics; Longevity: Selection; Nutrition; Pathology of Aging, Animal Models.
BIBLIOGRAPHY
Green, E. L., ed. Biology of the Laboratory Mouse. New York: McGraw-Hill, 1966.
Green, M. C., ed. Genetic Variants and Strains of Laboratory Mouse. Stuttgart: Gustav Fischer Verlag, 1981.
Sprott, R. L. ‘‘Development of Animal Models of Aging at the National Institute on Aging.’’ Neurobiology of Aging 12 (1991): 635–638.
Sprott, R. L. ‘‘Mouse and Rat Genotype Choices.’’ Aging Clinical Experimental Research 5 (1993): 249–252.
Rodents
Rodents
A rodent is any mammal that belongs to the order Rodentia, which includes most mammals equipped with continuously growing incisor teeth that are remarkably efficient for gnawing on tough plant matter. The name rodent comes from the Latin word rodere meaning “to gnaw.” Rodents live in virtually every habitat, often in close association with humans. This close association between rodents and humans is frequently detrimental to human interests, since rodents (especially rats and mice) eat huge quantities of stored food and spread serious, often fatal, diseases. There are far more members in the order Rodentia than in any other order of mammals. Nearly 40% of all mammal species belong to this order.
Some rodents such as beavers have been economically important. Others, such as guinea pigs, hamsters, and gerbils, are fun pets. However, most of the about 1,600 species (the exact number changes frequently as various groups of rodents are studied closely) play little role in human lives. Instead, they carry on their own lives in virtually every environment, rarely noticed by the humans around them.
Rodents are distinguished from other mammals primarily by their 16 teeth. Lagomorphs (rabbits and hares) also have continuously growing incisors, and they were, for many years, included among the rodents. But they have an additional pair of tiny incisors that grows just behind the big front teeth, so they are now classified in a separate order.
The two pairs of rodent incisors work together, like scissors. They grow continuously from birth and must regularly be used for gnawing to keep them worn down and sharp. They have a heavy coating of enamel on the front surface but none on the back. Because the enamel wears away more slowly than the rest of the tooth, a sharp, chisel-like edge is maintained on the gnawing teeth. If a rodent breaks one of its incisors, the animal usually soon dies because it cannot eat properly.
Unlike many mammals, rodents have no canine teeth. Instead, there is an empty space between the incisors and flat-topped cheek-teeth, or molars, at the side of the mouth. This space lets rodents suck in their cheeks or lips to shield their mouths and throats from chips flying from whatever material they are gnawing. When using their cheek-teeth to grind up the plant matter they have gnawed, rodents have special jaw muscles that keep their incisors out of the way.
Rodents are divided into three groups according to the way their jaw muscles and associated skull structures are arranged. This is very important because these muscles control gnawing.
The squirrel-like rodents (Sciuromorpha) have a very simple jaw muscle that extends onto the snout in front of the eye. This group includes the squirrels as well as such unsquirrel-like animals as beavers and pocket gophers. They are mostly found in the northern hemisphere.
The mouse-like or rat-like rodents (Myomorpha) have jaw muscles that anchor on the side of the nose. Because their jaw muscles are the most efficient, this group contains the most species and is found all over the world. It includes the mice, rats, voles, lemmings, and even the riverbank-dwelling muskrat. Two-thirds of all rodents belong to only one family in this group, the mice.
The cavy-like rodents (Caviomorpha) have very large cheekbones and muscles that anchor to the side of the face. This group includes the porcupines, as well as primarily South American mammals such as the cavy. Some fossil mammals in this group were as large as bears. The Old World members of this group are sometimes placed in a separate group called the porcupine-like rodents (Hystricomorpha).
Most rodents are very small, averaging less than 5 oz (150 g). However, the capybara, a large South American rodent, may weigh as much as 145 lb (66 kg). Rodents usually breed easily and quickly, producing large litters. This fact played a major role in their worldwide distribution. Genetic changes can develop into new species quite rapidly when animals breed so quickly. Such changes allowed rodents to take over many habitats that might not otherwise have been suitable. Rodents swim, glide, burrow, climb, and survive different uncomfortable climates.
KEY TERMS
Canines— Pointed teeth of most mammals, used for stabbing food. Rodents lack canine teeth.
Cheek-teeth— Molars and premolars, the grinding teeth located on the side of the mouth in rodents and many other mammals.
Incisors— The front cutting teeth of a mammal. In rodents, they grow continuously.
Rodents are known to carry disease-causing agents of at least 20 important human diseases including bubonic plague. About 500 years ago, at least 25 million people died in Europe from the “black death,” as the plague was called. The plague-causing bacteria (Yersinia pestis) were carried by fleas that were spread from rodents to people.
See also Agouti; Capybaras; Chinchilla; Chipmunks; Coypu; Deer mouse; Dormouse; Jerboas; Kangaroo rats; Mole-rats; Prairie dog.
Resources
BOOKS
Anthony, H.E. Field Book of North American Mammals. Kila, MT: Kessinger Publishing, 2005.
PERIODICALS
The International Mouse Mutagenesis Consortium. “Functional Annotation of Mouse Genome Sequences.” Science 291 (16 February 2001): 1251-1255.
Jean F. Blashfield
Rodents
Rodents
A rodent is any mammal that belongs to the order Rodentia, which includes most mammals equipped with continuously growing incisor teeth that are remarkably efficient for gnawing on tough plant matter . The name rodent comes from the Latin word rodere meaning "to gnaw." Rodents live in virtually every habitat , often in close association with humans. This close association between rodents and humans is frequently detrimental to human interests, since rodents (especially rats and mice ) eat huge quantities of stored food and spread serious, often fatal, diseases. There are far more members in the order Rodentia than in any other order of mammals. Nearly 40% of all mammal species belong to this order.
Some rodents such as beavers have been economically important. Others, such as guinea pigs , hamsters , and gerbils , are fun pets. However, most of the about 1,600 species (the exact number changes frequently as various groups of rodents are studied closely) play little role in human lives. Instead, they carry on their own lives in virtually every environment, rarely noticed by the humans around them.
Rodents are distinguished from other mammals primarily by their 16 teeth. Lagomorphs (rabbits and hares) also have continuously growing incisors, and they were, for many years, included among the rodents. But they have an additional pair of tiny incisors that grows just behind the big front teeth, so they are now classified in a separate order.
The two pairs of rodent incisors work together, like scissors. They grow continuously from birth and must regularly be used for gnawing to keep them worn down and sharp. They have a heavy coating of enamel on the front surface but none on the back. Because the enamel wears away more slowly than the rest of the tooth, a sharp, chisel-like edge is maintained on the gnawing teeth. If a rodent breaks one of its incisors, the animal usually soon dies because it cannot eat properly.
Unlike many mammals, rodents have no canine teeth. Instead, there is an empty space between the incisors and flat-topped cheek-teeth, or molars, at the side of the mouth. This space lets rodents suck in their cheeks or lips to shield their mouths and throats from chips flying from whatever material they are gnawing. When using their cheek-teeth to grind up the plant matter they have gnawed, rodents have special jaw muscles that keep their incisors out of the way.
Rodents are divided into three groups according to the way their jaw muscles and associated skull structures are arranged. This is very important because these muscles control gnawing.
The squirrel-like rodents (Sciuromorpha) have a very simple jaw muscle that extends onto the snout in front of the eye . This group includes the squirrels as well as such unsquirrel-like animals as beavers and pocket gophers . They are mostly found in the northern hemisphere.
The mouse-like or rat-like rodents (Myomorpha) have jaw muscles that anchor on the side of the nose. Because their jaw muscles are the most efficient, this group contains the most species and is found all over the world. It includes the mice, rats, voles , lemmings , and even the riverbank-dwelling muskrat . Two-thirds of all rodents belong to only one family in this group, the mice.
The cavy-like rodents (Caviomorpha) have very large cheekbones and muscles that anchor to the side of the face. This group includes the porcupines , as well as primarily South American mammals such as the cavy. Some fossil mammals in this group were as large as bears . The Old World members of this group are sometimes placed in a separate group called the porcupine-like rodents (Hystricomorpha).
Most rodents are very small, averaging less than 5 oz (150 g). However, the capybara, a large South American rodent, may weigh as much as 145 lb (66 kg). Rodents usually breed easily and quickly, producing large litters. This fact played a major role in their worldwide distribution. Genetic changes can develop into new species quite rapidly when animals breed so quickly. Such changes allowed rodents to take over many habitats that might not otherwise have been suitable. Rodents swim, glide, burrow, climb, and survive different uncomfortable climates.
Rodents are known to carry disease-causing agents of at least 20 important human diseases including bubonic plague . About 500 years ago, at least 25 million people died in Europe from the "black death," as the plague was called. The plague-causing bacteria (Yersinia pestis) were carried by fleas that were spread from rodents to people.
See also Agouti; Capybaras; Chinchilla; Chipmunks; Coypu; Deer mouse; Dormouse; Jerboas; Kangaroo rats; Mole-rats; Prairie dog.
Resources
books
Knight, Linsay. The Sierra Club Book of Small Mammals. San Francisco: Sierra Club Books, 1993.
periodicals
The International Mouse Mutagenesis Consortium. "Functional Annotation of Mouse Genome Sequences." Science 291 (February 16, 2001): 1251-1255.
Jean F. Blashfield
KEY TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .- Canines
—Pointed teeth of most mammals, used for stabbing food. Rodents lack canine teeth.
- Cheek-teeth
—Molars and premolars, the grinding teeth located on the side of the mouth in rodents and many other mammals.
- Incisors
—The front cutting teeth of a mammal. In rodents, they grow continuously.
Rodentia
rodent
ro·dent / ˈrōdnt/ • n. a gnawing mammal of an order (Rodentia) that includes rats, mice, squirrels, hamsters, porcupines, and their relatives, distinguished by strong constantly growing incisors and no canine teeth. They constitute the largest order of mammals.• adj. of or relating to mammals of this order.