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 for research in psychology, medicine, and other fields.
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Laboratory rats share origins with their cousins in domestication, the fancy rats. In 18th century Europe, wild Brown rats ran rampant and this infestation fueled the industry of rat-catching. Rat-catchers 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 was a popular sport which involved filling a pit with rats and timing how long it took for a terrier 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. 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.[1]
Over the years, rats have been used in many experimental studies, which have added to our understanding of genetics, diseases, the effects of drugs, 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.[1]
Domestic rats 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 brains, livers, kidneys, adrenal glands, and hearts 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,[2] 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.
Recent studies have shown that rats release a brain chemical, dopamine when they play. The study was conducted at Gettysburg College where holes were drilled into the skull of each experimentational rat and a tube was used to collect amounts of dopamine released.
Rat strains are generally not transgenic, or genetically modified, because the gene knockout and embryonic stem cell techniques that work in mice are relatively difficult in rats. This has disadvantaged many investigators, who regard many aspects of behavior and physiology in rats as more relevant to humans and easier to observe than in mice and who wish to trace their observations to underlying genes. As a result, many have been forced to study questions in mice that might be better pursued in rats. In October 2003, however, researchers succeeded in cloning two laboratory rats by nuclear transfer. So rats may begin to see more use as genetic research subjects. Much of the genome of Rattus norvegicus has been sequenced.[3]
A strain, 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. 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 genotypes are unnecessary or a population with genetic variation is required, and are usually referred to as stocks rather than strains.[4][5]
Wistar rats are an outbred strain of albino rats belonging to the species Rattus norvegicus. This strain was developed at the Wistar Institute in 1906 for use in biological and medical research, and is notably the first rat strain developed to serve as a model organism 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 Henry Donaldson, scientific administrator Milton J. Greenman, and genetic researcher/embryologist Helen Dean King.[6][7]
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.
The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research.[8][9][10][11] Its main advantage is its calmness and ease of handling.[12] This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley Animal Company) in Madison, Wisconsin. These rats were first bred in 1925. The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan Sprague Dawley) in January 1980.[13]
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.[14] These rats typically have increased tail to body length ratio compared with Wistar rats.
Biobreeding Diabetes Prone rats (or BBDP rat) rat is an inbred rat strain that spontaneously develops autoimmune Type 1 Diabetes. Like NOD mice, 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.[15]
Long-Evans rats are an outbred strain of rats 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, frequently in behavioral and obesity research.
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, capable of weighing up to 1 kilogram (2.2 lb)—more than twice the average weight.[16][17][18]
Obese Zucker rats have high levels of lipids and cholesterol in their blood, are resistant to insulin without being hyperglycemic, and gain weight from an increase in both the size and number of fat cells.[19] 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.[17][19]
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.[20] The more common ones are denoted as rnu (Rowett nude), fz (fuzzy), and shn (shorn).
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.[24]
Shaking rat Kawasaki (SRK) is an autosomal recessive mutant rat that has a short deletion in the RELN gene.[25] This results in the lowered expression of Reelin protein, essential for proper cortex lamination and cerebellum development. Its phenotype is similar to the widely researched reeler mouse. Shaking rat Kawasaki was first described in 1988.[26]
Routes of administration of injections in laboratory rats are mainly subcutaneous, intraperitoneal, intravenous and intramuscular.[27]
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