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The albino laboratory rat with its red eyes and white fur is an iconic model organism for scientific research in a variety of fields.

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.

Contents

History

Wild rats that were used in rat-baiting were eventually bred domestically, producing the albino white lab rat known today.

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 would be 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.

A lab rat in a Morris water maze.

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]

Strains

A strain, in reference to rodents, is a group in which all members are 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. The opposite, outbred strains, are used when identical genotypes are unneccessary or a random population is required, and are more defined as stocks as opposed to strains.[4]

Wistar rat

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.[5][6]

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.[7][8][9][10] Its main advantage is its calmness and ease of handling.[11] This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley Animal Company) in Madison, Wisconsin. The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan Sprague Dawley) in January 1980.[12]

The average litter size of the Sprague Dawley rat is 10.5. The adult body weight is 250–300g for females, and 450–520g for males. The typical life span is 2.5–3.5 years.[13] These rats typically have increased tail to body length ratio compared with Wistar rats.

Biobreeding rat

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 T1D pathogenesis.[14]

Long-Evans rat

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 rat

Rat diabetic.jpg

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.[15][16][17]

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.[18] Obesity in Zucker rats is primarily linked to their hyperphagic nature, an excessive hunger, however food intake does not fully explain the hyperlipidemia or overall body composition.[16][18]

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.[19] 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. The lack of this organ severely compromises their immune system, infections of the respiratory tract and eye increasing the most dramatically. [20]
  • 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. [21]
  • Shorn rats were bred from Sprague Dawley rats in Connecticut in 1998.[22] 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. [23]

Shaking rat Kawasaki

The Shaking rat Kawasaki lacks functional RELN gene that encodes reelin, a protein essential for proper cortex lamination and cerebellum development. Its phenotype is similar to the widely researched reeler mouse.

See also

References

  1. ^ a b Krinke, George J. (June 15, 2000). "History, Strains and Models". The Laboratory Rat (Handbook of Experimental Animals). Gillian R. Bullock (series ed.), Tracie bunton (series ed.). Academic Press. pp. 3–16. ISBN 012426400X. 
  2. ^ "43rd Annual Pathology of Laboratory Animals Course". http://www.afip.org/vetpath/POLA/POLA96/oldrats.txt. 
  3. ^ "Genome project". www.ensemble.org. http://www.ensembl.org/Rattus_norvegicus/index.html. Retrieved 2007-02-17. 
  4. ^ "Rules and Guidelines for Nomenclature of Mouse and Rat Strains". http://www.informatics.jax.org/mgihome/nomen/strains.shtml#oacc. 
  5. ^ *Clause, B. T. (1998). The Wistar Institute Archives: Rats (Not Mice) and History, Mendel Newsletter February, 1998.
  6. ^ "The Wistar Institute:History". The Wistar Institute. 2007. http://www.wistar.org/about_wistar/history.html. Retrieved 2008-11-09. 
  7. ^ Drachman RH, Root RK, Wood WB Jr. (1966). "Studies on the effect of experimental nonketotic diabetic mellitus on antibacterial defense". J Exp Med 124: 227–40. doi:10.1084/jem.124.2.227. PMID 4380670. 
  8. ^ Hsu CC, Lai SC (2007). "Matrix metalloproteinase-2, -9 and -13 are involved in fibronectin degradation of rat lung granulomatous fibrosis caused by Angiostrongylus cantonensis". Int J Exp Pathol 88: 437–43. doi:10.1111/j.1365-2613.2007.00554.x. PMID 18039280. 
  9. ^ Horiuchi N, Suda T, Sasaki S, Takahashi H, Shimazawa E, Ogata E. (1976). "Absence of regulatory effects of 1alpha25-dihydroxyvitamin D3 on 25-hydroxyvitamin D metabolism in rats constantly infused with parathyroid hormone". Biochem Biophys Res Commun 73: 869–75. doi:10.1016/0006-291X(76)90202-3. PMID 15625855. 
  10. ^ Sukov W, Barth DS (1998). "Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex". J Neurophysiol 79: 2875–84. PMID 9636093. 
  11. ^ ""Online Medical Dictionary"". 1998-12-12. http://cancerweb.ncl.ac.uk/cgi-bin/omd?rats,+sprague-dawley. Retrieved 2007-12-15. 
  12. ^ "Harlan Sprague Dawley". http://www.harlan.com/models/spraguedawley.asp. Retrieved 2007-12-15. 
  13. ^ Ace Animals website Retrieved on 2008-3-15.
  14. ^ Mordes JP, Poussier P, Blankenhorn EP, Greiner DL: Rat models of type 1 diabetes: Genetics, environment and autoimmunity. Boca Raton, CRC Press, 2007
  15. ^ Kurtz, TW; RC Morris and HA Pershadsingh (1989). "The Zucker fatty rat as a genetic model of obesity and hypertension". Hypertension (Dallas, Texas: American Heart Association) 13 (6): 896–901. ISSN 1524-4563. http://hyper.ahajournals.org/cgi/reprint/13/6/896.pdf. Retrieved 2008-12-06. 
  16. ^ a b Davis, Amy J. (January, 1997). "The Heart of a Zucker". Research PennState 18 (1). http://www.rps.psu.edu/jan97/zucker.html. Retrieved 2008-12-06. 
  17. ^ Takaya K, Ogawa Y, Isse N, Okazaki T, Satoh N, Masuzaki H, Mori K, Tamura N, Hosoda K, Nakao K. (1996). "Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats". Biochem Biophys Res Commun. 225: 75–83. PMID 8769097. 
  18. ^ a b Kava, Ruth; M. R. C. Greenwood and P. R. Johnson (1990). "Zucker (fa/fa) Rat". ILAR Journal (Institute for Laboratory Animal Research) 32 (3). http://dels.nas.edu/ilar_n/ilarjournal/32_3/32_3Zuckerfafa.shtml. Retrieved 2008-12-06. 
  19. ^ Kim H, Panteleyev AA, Jahoda CA, Ishii Y, Christiano AM. Genomic organization and analysis of the hairless gene in four hypotrichotic rat strains. Mamm Genome. 2004 Dec;15(12):975-81.
  20. ^ Festing MFW, D May, TA Connors, D Lovell, S Sparrow. 1978. An athymic nude mutation in the rat. Nature. 274. 365-366.
  21. ^ Ferguson, Frederick G, Et Al. Three Variations of Hairlessness Associated with Albanism in the Laboratory Rat. Laboratory Animal Science Vol.29 P. 459-465 yr. 1979
  22. ^ Moemeka, A. N., Hildebrandt, A.L., Radaskiewicz, P., & King, T. R. (1998). Shorn (shn): a new mutation causing hypotrichosis in the Norway rat. The Journal of Heredity, 89, 257-260 .
  23. ^ D’Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000). "Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat". Human Molecular Genetics 9: 645–651. PMID 10699188. 

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