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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 Alzheimers 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 attractiveor less objectionableas 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): 635638.

Sprott, R. L. Mouse and Rat Genotype Choices. Aging Clinical Experimental Research 5 (1993): 249252.

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rodent

rodent, member of the mammalian order Rodentia, characterized by front teeth adapted for gnawing and cheek teeth adapted for chewing. The Rodentia is by far the largest mammalian order; nearly half of all mammal species are rodents. They are worldwide in distribution and are found in almost every terrestrial and freshwater habitat, from the shores of the Arctic Ocean to the hottest deserts. They are variously adapted for running, jumping, climbing, burrowing, swimming, and gliding. Many of them have dexterous forepaws, which they use as hands while sitting on their haunches in a position characteristic of many rodents. The great majority are under a few inches in length; the largest, the capybara, is about 4 ft (120 cm) long and 20 in. (50 cm) high at the shoulder.

Characteristics of Rodents

Rodents have enlarged, chisel-shaped upper and lower front incisors that grow throughout their lives. These have hard enamel on the front surface and soft dentine on the back surface, so that unequal wear keeps the chisel edge sharp. There is a gap between the front teeth and the cheek teeth. When the lower jaw is in a forward position, for gnawing, the upper and lower incisors are in contact but the upper and lower cheek teeth are not; thus, wear on the cheek teeth is avoided. The cheeks are drawn in behind the incisors when the animal is gnawing, so that bits of hard material cannot be swallowed. When the lower jaw is pulled back into the chewing position, only the cheek teeth make contact.

Types of Rodents

The approximately 4,000 rodent species are divided on the basis of their anatomy into three well-defined groups, or suborders, and more than 30 families. The Sciuromorpha, or squirrellike rodents, include the various species of squirrel, chipmunk, marmot, woodchuck (or ground hog), prairie dog, gopher (or pocket gopher), pocket mouse, kangaroo rat, and beaver. The Myomorpha, or mouselike rodents, include a great variety of mouse and rat species, as well as species of hamster, lemming, vole, muskrat, gerbil, dormouse, and jerboa. This is the largest rodent group. The Hystricomorpha, or porcupinelike rodents, include the porcupine, capybara, nutria (or coypu), agouti, cavy (including the domestic guinea pig), mara, and chinchilla, as well as many species whose common names include the term rat (e.g., the South American bush rat).

Rabbits and hares were once classified as rodents because of their large, chisel-shaped incisors. However, they are quite distinct anatomically and have a long, separate evolutionary history; they are now classified in an order of their own, the Lagomorpha. Using DNA analyses as evidence, some scientists believe that the some other groups of rodents have descended from different ancestors and should thus be placed in orders of their own.

See also mountain beaver, ground squirrel, flying squirrel, pack rat, bandicoot rat, and jumping mouse.

Bibliography

See Sir J. R. Ellerman, The Families and Genera of Living Rodents (2 vol., 1940, repr. 1965); B. S. Vindgradov and A. I. Argiropulo, Key to Rodents (tr. 1968).

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Rodentia

Rodentia (rodents; simplicidentata; infraclass Eutheria, cohort Glires) An order of herbivorous or scavenging mammals in which the incisors are reduced to one pair in each jaw (hence the name ‘Simplicidentata’). The incisors have enamel on one surface only and grow continually so that by gnawing they are simultaneously sharpened and kept at a constant length. There is a wide diastema, the second incisors, canines, and first premolars being absent, and the remaining premolars and molars are usually similar in shape. Folds of skin can be taken into the diastema to seal off the mouth into two compartments: material taken into the mouth is not necessarily swallowed. In some rodents these skin folds are developed into cheek pouches. The jaw muscles are large and divided into three parts attached so as to permit a forward and backward jaw movement. The three suborders (Sciuromorpha, Myomorpha, and Hystricomorpha) are distinguished partly by the arrangement of the jaw muscles. Apart from the modifications to the jaws and teeth, rodents are rather unspecialized. Limbs usually are pentadactyl and clawed. Hind limbs are commonly longer than fore limbs. The digits of the fore limbs are used by many species for handling food. Gait is plantigrade or semi-plantigrade although many species are saltatory. Rodents emerged from eutherian stock during the late Cretaceous or Palaeocene and have shown little tendency to evolve to large size. Today they are distribute throughout the world. There are 1500–2000 species, so that rodents account for nearly half of all mammal species.

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Rodentia

Rodentia An order of mammals characterized by a single pair of long curved incisors in each jaw. These teeth are specialized for gnawing: they continue growing throughout life and have enamel only on the front so that they wear to a chisel-shaped cutting edge. Rodents often breed throughout the year and produce large numbers of quickly maturing young. The order includes the squirrels, beavers, rats, mice, and porcupines.

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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.

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rodent

rodent Any member of the vast order Rodentia, the most numerous and widespread of all mammals, characterized by a pair of gnawing incisor teeth in both the upper and lower jaws. Numbering close to 2000 species, including rats, mice, squirrels, beaver, dormice, porcupines, and guinea pigs, rodents live throughout the world. Most are small and light.

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rodent

rodent gnawing, belonging to the Rodentia. XIX. — L. rōdēns, -ent-, prp. of rōdere gnaw; see -ENT.

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rodent

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•applicant • supplicant • communicant •lubricant • desiccant • intoxicant •gallant, talent •appellant, propellant, propellent, repellent, water-repellent •resemblant •assailant, inhalant •sealant • sibilant • jubilant •flagellant • vigilant • pestilent •silent •Solent, volant •coolant • virulent • purulent •ambulant, somnambulant •coagulant • crapulent • flatulent •feculent • esculent • petulant •stimulant • flocculent • opulent •postulant • fraudulent • corpulent •undulant •succulent, truculent •turbulent • violent • redolent •indolent • somnolent • excellent •insolent • nonchalant •benevolent, malevolent, prevalent •ambivalent, equivalent •garment • clement • segment •claimant, clamant, payment, raiment •ailment •figment, pigment •fitment • aliment • element •oddment •dormant, informant •moment • adamant • stagnant •lieutenant, pennant, subtenant, tenant •pregnant, regnant •remnant • complainant •benignant, indignant, malignant •recombinant • contaminant •eminent •discriminant, imminent •dominant, prominent •illuminant, ruminant •determinant • abstinent •continent, subcontinent •appurtenant, impertinent, pertinent •revenant •component, deponent, exponent, opponent, proponent •oppugnant, repugnant •immanent •impermanent, permanent •dissonant • consonant • alternant •covenant • resonant • rampant •discrepant • flippant • participant •occupant • serpent •apparent, arrant, transparent •Arendt •aberrant, deterrent, errant, inherent, knight-errant •entrant •declarant, parent •grandparent • step-parent •godparent •flagrant, fragrant, vagrant •registrant • celebrant • emigrant •immigrant • ministrant • aspirant •antiperspirant • recalcitrant •integrant • tyrant • vibrant • hydrant •migrant, transmigrant •abhorrent, torrent, warrant •quadrant • figurant • obscurant •blackcurrant, concurrent, currant, current, occurrent, redcurrant •white currant • cross-current •undercurrent •adherent, coherent, sederunt •exuberant, protuberant •reverberant • denaturant •preponderant • deodorant •different, vociferant •belligerent, refrigerant •accelerant • tolerant • cormorant •itinerant • ignorant • cooperant •expectorant • adulterant •irreverent, reverent •nascent, passant •absent •accent, relaxant •acquiescent, adolescent, albescent, Besant, coalescent, confessant, convalescent, crescent, depressant, effervescent, erubescent, evanescent, excrescent, flavescent, fluorescent, immunosuppressant, incandescent, incessant, iridescent, juvenescent, lactescent, liquescent, luminescent, nigrescent, obsolescent, opalescent, pearlescent, phosphorescent, pubescent, putrescent, quiescent, suppressant, tumescent, turgescent, virescent, viridescent •adjacent, complacent, obeisant •decent, recent •impuissant, reminiscent •Vincent • puissant •beneficent, maleficent •magnificent, munificent •Millicent • concupiscent • reticent •docent •lucent, translucent •discussant, mustn't •innocent •conversant, versant •consentient, sentient, trenchant •impatient, patient •ancient • outpatient •coefficient, deficient, efficient, proficient, sufficient •quotient • patent •interactant, reactant •disinfectant, expectant, protectant •repentant • acceptant •contestant, decongestant •sextant •blatant, latent •intermittent •assistant, coexistent, consistent, distant, equidistant, existent, insistent, persistent, resistant, subsistent, water-resistant •instant •cohabitant, habitant •exorbitant • militant • concomitant •impenitent, penitent •palpitant • crepitant • precipitant •competent, omnicompetent •irritant • incapacitant • Protestant •hesitant • visitant • mightn't • octant •remontant • constant •important, oughtn't •accountant • potent •mutant, pollutant •adjutant • executant • disputant •reluctant •consultant, exultant, resultant •combatant • omnipotent • impotent •inadvertent •Havant, haven't, savant, savante •advent •irrelevant, relevant •pursuivant • solvent • convent •adjuvant •fervent, observant, servant •manservant • maidservant •frequent, sequent •delinquent • consequent •subsequent • unguent • eloquent •grandiloquent, magniloquent •brilliant • poignant • hasn't •bezant, omnipresent, peasant, pheasant, pleasant, present •complaisant • malfeasant • isn't •cognizant • wasn't • recusant •doesn't

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