Laboratory rat
Encyclopedia
A laboratory rat is a rat of the species Rattus norvegicus which is bred and kept for scientific research. Laboratory rats have served as an important animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...

 for research in psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

, medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

, and other fields.

Origins

Laboratory rats share origins with their cousins in domestication, the fancy rat
Fancy rat
The fancy rat is a domesticated brown rat , which is the most common type of pet rat. The name fancy rat derives from the idea of animal fancy or the phrase "to fancy" ....

s. In 18th century Europe, wild Brown rats ran rampant and this infestation fueled the industry of rat-catching. Rat-catcher
Rat-catcher
Rat-catching is the occupation of catching rats as a form of pest control. In developed countries the role may be merged with, or the title inflated to, Pest Control Operative or Pest Technician....

s would not only make money by trapping the rodents, but also by turning around and selling them for food, or more importantly, for rat-baiting
Rat-baiting
Rat-baiting is a blood sport involving the baiting of rats in a pit. Unlike most varieties of baiting, there were usually more rats than dogs involved in an exhibition.-History:...

.

Rat-baiting
Rat-baiting
Rat-baiting is a blood sport involving the baiting of rats in a pit. Unlike most varieties of baiting, there were usually more rats than dogs involved in an exhibition.-History:...

 was a popular sport which involved filling a pit with rats and timing how long it took for a terrier
Terrier
A terrier is a dog of any one of many breeds or landraces of terrier type, which are typically small, wiry, very active and fearless dogs. Terrier breeds vary greatly in size from just a couple of pounds to over 70 pounds and are usually categorized by size or function...

 to kill them all. Over time, breeding the rats for these contests produced variations in color, notably the albino and hooded varieties. The first time one of these albino mutants was brought into a laboratory for a study was in 1828, in an experiment on fasting
Fasting
Fasting is primarily the act of willingly abstaining from some or all food, drink, or both, for a period of time. An absolute fast is normally defined as abstinence from all food and liquid for a defined period, usually a single day , or several days. Other fasts may be only partially restrictive,...

. Over the next 30 years rats were used for several more experiments and eventually the laboratory rat became the first animal domesticated for purely scientific reasons.

Use in research

Over the years, rats have been used in many experimental studies, which have added to our understanding of genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

, disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

s, the effects of drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

s, and other topics in health and medicine. Laboratory rats have also proved valuable in psychological studies of learning and other mental processes. The historical importance of this species to scientific research is reflected by the amount of literature on it, roughly 50% more than that on mice.

Domestic rats
Fancy rat
The fancy rat is a domesticated brown rat , which is the most common type of pet rat. The name fancy rat derives from the idea of animal fancy or the phrase "to fancy" ....

 differ from wild rats in many ways: They are calmer and less likely to bite, they can tolerate greater crowding, they breed earlier and produce more offspring, and their brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

s, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

s, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s, adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s, and heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

s are smaller.

Scientists have bred many strains or "lines" of rats specifically for experimentation. Most are derived from the albino Wistar rat, which is still widely used. Other common strains are the Sprague Dawley, Fischer 344, Holtzman albino strains, the Long-Evans, and Lister black hooded rats. Inbred strains are also available but are not as commonly used as inbred mice.

Rat strains are generally not transgenic, or genetically modified, because the gene knockout
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...

 and embryonic stem cell
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...

 techniques that work in mice are relatively difficult in rats. This has disadvantaged many investigators, who regard many aspects of behavior
Behavior
Behavior or behaviour refers to the actions and mannerisms made by organisms, systems, or artificial entities in conjunction with its environment, which includes the other systems or organisms around as well as the physical environment...

 and physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 in rats as more relevant to humans and easier to observe than in mice and who wish to trace their observations to underlying gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s. As a result, many have been forced to study questions in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...

 that might be better pursued in rats. In October 2003, however, researchers succeeded in cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...

 two laboratory rats by nuclear transfer
Somatic cell nuclear transfer
In genetics and developmental biology, somatic-cell nuclear transfer is a laboratory technique for creating a clonal embryo, using an ovum with a donor nucleus . It can be used in embryonic stem cell research, or, potentially, in regenerative medicine where it is sometimes referred to as...

. So rats may begin to see more use as genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 research subjects. Much of the genome of Rattus norvegicus
Rat genome database
The Rat Genome Database is a collection of genetic and genomic information on the rat. Development and maintenance of RGD began in 1995 and is funded by the United States National Institutes of Health and hosted at the Medical College of Wisconsin...

 has been sequenced
Full genome sequencing
Full genome sequencing , also known as whole genome sequencing , complete genome sequencing, or entire genome sequencing, is a laboratory process that determines the complete DNA sequence of an organism's genome at a single time...

.

Strains

A strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

, in reference to rodents, is a group in which all members are as nearly as possible genetically identical. In rats, this is accomplished through inbreeding
Inbreeding
Inbreeding is the reproduction from the mating of two genetically related parents. Inbreeding results in increased homozygosity, which can increase the chances of offspring being affected by recessive or deleterious traits. This generally leads to a decreased fitness of a population, which is...

. By having this kind of population, it is possible to conduct experiments on the roles of genes, or conduct experiments that exclude variations in genetics as a factor. By contrast, outbred populations are used when identical genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...

s are unnecessary or a population with genetic variation is required, and are usually referred to as stocks rather than strains.

Wistar rat

Wistar rats are an outbred strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 of albino rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s belonging to the species Rattus norvegicus. This strain was developed at the Wistar Institute
Wistar Institute
The Wistar Institute is a biomedical center, with a focus on cancer research and vaccine development. It is located in the University City section of Philadelphia, Pa...

 in 1906 for use in biological and medical research, and is notably the first rat strain developed to serve as a model organism
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...

 at a time when laboratories primarily used Mus musculus, or the common House mouse. More than half of all laboratory rat strains are descended from the original colony established by physiologist
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 Henry Donaldson, scientific administrator Milton J. Greenman, and genetic researcher
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

/embryologist Helen Dean King
Helen Dean King
Helen Dean King was an American biologist. Born at Owego, N. Y., she graduated from Vassar College in 1892 and in 1899 received her doctorate in philosophy from Bryn Mawr College, where she was fellow and student assistant in biology from 1897 to 1904...

.

The Wistar rat is currently one of the most popular rat strains used for laboratory research. It is characterized by its wide head, long ears, and having a tail length that is always less than its body length. The Sprague Dawley rat and Long-Evans rat strains were developed from Wistar rats. Wistar rats are more active than other strains like Sprague Dawley rats.

Sprague Dawley rat

The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. Its main advantage is its calmness and ease of handling. This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley Animal Company) in Madison, Wisconsin
Madison, Wisconsin
Madison is the capital of the U.S. state of Wisconsin and the county seat of Dane County. It is also home to the University of Wisconsin–Madison....

. These rats were first bred in 1925. The breeding facilities were purchased first by Gibco and then by Harlan
Harlan (company)
Harlan Sprague Dawley Inc. is one of the world's leading suppliers of animals and other services to laboratories for the purpose of animal testing...

 (now Harlan Sprague Dawley) in January 1980.

The average litter size of the Sprague Dawley rat is 10.5. The adult body weight is 250–300 g for females, and 450–520 g for males. The typical life span is 2.5–3.5 years. These rats typically have increased tail to body length ratio compared with Wistar rats.

Biobreeding rat

Biobreeding Diabetes Prone rats (or BBDP
Biobreeding rat
Biobreeding rat also known as the BB or BBDP rat is an inbred laboratory rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like the NOD mice, BB rats are used as an animal model for Type 1 diabetes...

 rat) rat is an inbred rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like NOD mice
NOD mice
Non-obese diabetic or NOD mice, like the Biobreeding rat, are used as an animal model for type 1 diabetes.- History :Non-obese diabetic mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus...

, BB rats are used as an animal model for Type 1 diabetes. The strain re-capitulates many of the features of human type 1 diabetes, and has contributed greatly to the research of T1DM pathogenesis.

Long-Evans rat

Long-Evans rats are an outbred strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 of rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s belonging to the species Rattus norvegicus. This strain was developed by Drs. Long and Evans in 1915 by crossing several Wistar females with a wild gray male. Long Evans rats are white with a black hood, or occasionally white with a brown hood. They are utilized as a multipurpose model organism
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...

, frequently in behavioral and obesity research.

Zucker rat

Zucker rats were bred to be a genetic model for research on obesity and hypertension. They are named after Lois M. Zucker and Theodore F. Zucker, pioneer researchers in the study of the genetics of obesity. There are two types of Zucker rat: a lean Zucker rat, denoted as the dominant trait (Fa/Fa) or (Fa/fa); and the characteristically obese (or fatty) Zucker rat, which is actually a recessive trait (fa/fa) of the leptin receptor
Leptin receptor
Leptin receptor also known as LEP-R is a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin...

, capable of weighing up to 1 kilograms (2.2 lb)—more than twice the average weight.

Obese Zucker rats have high levels of lipids
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...

 and cholesterol
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...

 in their blood, are resistant to insulin
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...

 without being hyperglycemic, and gain weight from an increase in both the size
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...

 and number
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....

 of fat cells
Adipocyte
However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...

. Obesity in Zucker rats is primarily linked to their hyperphagic nature, and excessive hunger; however, food intake does not fully explain the hyperlipidemia or overall body composition.

Hairless rats

Hairless lab rats provide researchers with valuable data regarding compromised immune systems and genetic kidney diseases. It is estimated that there are over twenty-five genes that cause recessive hairlessness in laboratory rats. The more common ones are denoted as rnu (Rowett nude), fz (fuzzy), and shn (shorn).
  • Rowett nudes, first identified in 1953 in Scotland, have no thymus
    Thymus
    The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

    . The lack of this organ severely compromises their immune system, infections of the respiratory tract and eye increasing the most dramatically.

  • Fuzzy rats were identified in 1976 in a Pennsylvanian lab. The leading cause of death among fz/fz rats is ultimately a progressive kidney failure that begins around the age of one.

  • Shorn rats were bred from Sprague Dawley rats in Connecticut in 1998. They also suffer from severe kidney problems.

RCS rats

The Royal College of Surgeons (RCS) rat is the first known animal with inherited retinal degeneration. Although the genetic defect was not known for many years, it was identified in the year 2000 to be a mutation in the gene Mertk. This mutation results in defective retinal pigment epithelium phagocytosis of photoreceptor outer segments.

Shaking rat Kawasaki

Shaking rat Kawasaki (SRK) is an autosomal recessive mutant rat that has a short deletion in the RELN gene. This results in the lowered expression of Reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...

 protein, essential for proper cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

 lamination and cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

 development. Its phenotype is similar to the widely researched reeler
Reeler
A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by profound hypoplasia of the mouse's cerebellum, in which the normal cerebellar folia are missing. The mutation is autosomal and recessive....

 mouse. Shaking rat Kawasaki was first described in 1988.

Injection procedures

Routes of administration of injections in laboratory rats are mainly subcutaneous, intraperitoneal, intravenous and intramuscular.

See also

  • Animal testing on rodents
    Animal testing on rodents
    Rodents are commonly used in animal testing, particularly guinea pigs, hamsters, gerbils, rats, and mice.-The statistics:In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents were used...

  • Biobreeding rat
    Biobreeding rat
    Biobreeding rat also known as the BB or BBDP rat is an inbred laboratory rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like the NOD mice, BB rats are used as an animal model for Type 1 diabetes...

  • Knockout rat
    Knockout rat
    A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation used for academic and pharmaceutical research. Knockout rats can mimic human diseases and are important tools for studying gene function and for drug discovery and development...

  • Morris water maze
    Morris water maze
    The Morris water navigation task is a behavioral procedure widely used in behavioral neuroscience to study spatial learning and memory. It was developed by neuroscientist Richard G...

  • Rat genome database
    Rat genome database
    The Rat Genome Database is a collection of genetic and genomic information on the rat. Development and maintenance of RGD began in 1995 and is funded by the United States National Institutes of Health and hosted at the Medical College of Wisconsin...

  • Brattleboro rat
    Brattleboro rat
    The Brattleboro rat is a strain of laboratory rat descended from a litter born in West Brattleboro, Vermont in 1961 without the ability to produce the hormone vasopressin, which helps control kidney function. The rats' lack of vasopressin was the result of a naturally occurring genetic mutation.The...


External links

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