{{Short description|Rat used for scientific research}} {{Redirect|Lab rat}} {{Use DMY dates|date=October 2023}} [[File:Sister ratties 2.jpg|thumb|The [[Albinism in biology|albino]] laboratory rat with its red eyes and white fur is an iconic model organism for scientific research in a variety of fields.]]
'''Laboratory rats''' or '''lab rats''' are [[strain (biology)|strain]]s of the [[rat]] subspecies ''[[Rattus norvegicus domestica]]'' (Domestic Norwegian rat) which are bred and kept for [[scientific research]]. While [[Animal testing on rodents|less commonly used]] for research than [[laboratory mice]], rats have served as an important [[animal model]] for research in [[psychology]] and [[biomedical science]],<ref name="Vandenbergh">{{cite journal |last=Vandenbergh |first=J. G. |title=Use of House Mice in Biomedical Research |journal=[[ILAR Journal]] |date=1 January 2000 |volume=41 |issue=3 |pages=133–135 |doi=10.1093/ilar.41.3.133 |doi-access=free}}</ref> and "lab rat" is commonly used as an idiom for a test subject.
==Origins of rat breeding== [[File:Rat Killing Dog.jpg|thumb|[[Rat-baiting]]]] In 18th-century [[Europe]], wild brown rats (''[[Rattus norvegicus]]'') ran rampant and this infestation fueled the industry of rat-catching. [[Rat-catcher]]s would not only make money by trapping the rodents, but also by selling them [[rat meat|for food]] or, more commonly, 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 may have produced color variations, notably the [[albino rat|albino]] and [[hooded rat|hooded]] varieties. The first time one of these albino mutants was brought into a laboratory for a study was in 1828 for 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.<ref name="krinke">{{cite book |first1=George J |last1=Krinke |first2=Gillian R. |last2=Bullock |first3=G. |last3=Krinke |title=The Laboratory Rat (Handbook of Experimental Animals) |publisher=[[Academic Press]] |date=15 June 2000 |pages=3–16 |chapter=History, Strains and Models |isbn=012426400X}}</ref> [[File:WT and TK rat photo.jpg|thumb|right|[[hooded rat|Hooded]]|alt=Two [[hooded rat]]s]] In [[Japan]], there was a widespread practice of keeping rats as a domesticated pet during the [[Edo period]] and in the 18th century guidebooks on keeping domestic rats were published by [[Youso Tamanokakehashi]] (1775) and [[Chingan Sodategusa]] (1787). [[Genetic analysis]] of 117 [[albino rat]] [[strain (biology)|strain]]s collected from all parts of the world carried out by a team led by [[Takashi Kuramoto]] at [[Kyoto University]] in 2012 showed that the albinos descended from hooded rats and all the albinos descended from a single ancestor.<ref name="Kuramoto">{{cite web |url= http://www.shigen.nig.ac.jp/shigen/news/n_letter/2012/newsletter_v8_n11En.html |title=Origin of Albino Laboratory Rats |last=Kuramoto |first=Takashi |date=November 2012 |work=[[Bio Resource Newsletter]] |publisher=[[National Institute of Genetics]] |access-date=20 December 2013}}</ref> As there is evidence that the hooded rat was known as the "Japanese rat" in the early 20th century, Kuramoto concluded that one or more Japanese hooded rats might have been brought to Europe or the Americas and an albino rat that emerged as a product of the breeding of these hooded rats was the common ancestor of all the albino laboratory rats in use today.<ref name="Kuramoto" />
==Use in research== [[File:Cut_Rat.jpg|right|thumb|[[Dissection]]]] The rat found early use by [[research lab]]s in five areas: [[W. S. Small]] suggested that rats could measure the rate of learning in a [[maze]]; a suggestion employed by [[John B. Watson]] for his [[Ph.D. dissertation]] in 1903.<ref>[[John B. Watson]] (1903) "Psychical development of the white rat", Ph.D. University of Chicago</ref> The first rat colony in America used for nutrition research was started in January 1908 by [[Elmer McCollum]]<ref>{{cite journal |last=Day |first=H. G. |title=Elmer Verner McCollum |journal=[[Biographical Memoirs of the National Academy of Sciences]] |volume=45 |pages=263–335 |date=1974 |pmid=11615648}}</ref> and then, nutritive requirements of rats were used by [[Thomas Burr Osborne (chemist)|Thomas Burr Osborne]] and [[Lafayette Mendel]] to determine the details of [[Protein (nutrient)|protein nutrition]]. The [[Reproduction|reproductive function]] of rats was studied at the Institute for Experimental Biology at the [[University of California, Berkeley]] by [[Herbert McLean Evans]] and Joseph A. Long.<ref>{{cite book |last1= Long |first1=J. A. |last2=Evans H. M. |date=1922 |title=The oestrous cycle in the rat and its associated phenomena |url=https://archive.org/details/06120800R.nlm.nih.gov |publisher=[[University of California Press]]}}</ref> The [[genetics]] of rats was studied by [[William Ernest Castle]] at the [[Bussey Institution|Bussey Institute]] of [[Harvard University]] until it closed in 1994. Rats have long been used in [[cancer research]]; for instance at the [[Francis C. Wood|Crocker Institute for Cancer Research]].<ref>{{cite book |first1=Mark A. |last1=Suckow |first2=Steven H. |last2=Weisbroth |first3=Craig L. |last3=Franklin |date=2005 |chapter=Chapter one: Historical Foundations |title=The Laboratory Rat |isbn=0080454321}}</ref>
[[File:MorrisWaterMaze.jpg|left|thumb|[[Morris water navigation test]]]]
The historical importance of this species to scientific research is reflected by the amount of [[scientific literature|literature]] on it: roughly 50% more than that on [[Laboratory mouse|laboratory mice]].<ref name="krinke" /> Laboratory rats are frequently subject to [[dissection]] or [[microdialysis]] to study internal effects on organs and the brain, such as for [[cancer]] or [[pharmacological]] research. Laboratory rats not sacrificed may be [[euthanized]] or, in some cases, [[Pet adoption|become pets]].
[[File:Sleep-deprivation-flowerpot-technique-jepoirrier.jpg|thumb|Deprivation of [[Rapid eye movement sleep|REM sleep]] using the [[flowerpot technique]]]]
[[Domestic rat]]s differ from wild rats (various spp. of [[Rodentia]]) in many ways: they are calmer and significantly less likely to bite, they can tolerate greater crowding, they breed earlier and produce more offspring, and their [[brain]]s, [[liver]]s, [[kidney]]s, [[adrenal gland]]s, and [[heart]]s are smaller.
Scientists have bred many [[strain (biology)|strain]]s 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]],<ref>{{cite web |url= http://www.afip.org/vetpath/POLA/POLA96/oldrats.txt |title=43rd Annual Pathology of Laboratory Animals Course |access-date=15 September 2008 |archive-url= https://archive.today/20000816215322/http://www.afip.org/vetpath/POLA/POLA96/oldrats.txt |archive-date=16 August 2000 |url-status=dead}}</ref> [[Holtzman rat|Holtzman]] albino strains, [[Long–Evans]], and [[Lister rat|Lister]] black hooded rats. [[Inbred strain]]s are also available, but are not as commonly used as inbred mice.
Much of the [[Rat genome database|genome of ''Rattus norvegicus'']] has been [[Full genome sequencing|sequenced]].<ref>{{cite web |url= http://www.ensembl.org/Rattus_norvegicus/index.html |title=Genome Project |access-date=17 February 2007 |work=[[Ensembl]]}}</ref> In October 2003, researchers succeeded in [[cloning]] two laboratory rats by [[Somatic cell nuclear transfer|nuclear transfer]]. This was the first in a series of developments that have begun to make rats tractable as [[Genetics|genetic]] research subjects, although they still lag behind mice, which lend themselves better to the [[embryonic stem cell]] techniques typically used for [[genetic engineering|genetic manipulation]]. Many investigators who wish to trace observations on [[behavior]] and [[physiology]] to underlying [[gene]]s regard aspects of these in rats as more relevant to humans and easier to observe than in mice, giving impetus to the development of genetic research techniques applicable to rats.
[[File:Intelligence-Augmented-Rat-Cyborgs-in-Maze-Solving-pone.0147754.s004.ogv|thumb|Traversing complex terrain under the influence of [[electrode]] inputs to its brain]]
A 1972 study compared [[neoplasms]] in Sprague Dawleys from six different [[laboratory animal supplier|commercial suppliers]] and found highly significant differences in the incidences of [[endocrine]] and [[mammary]] tumors. There were even significant variations in the incidences of [[adrenal medulla]] tumors among rats from the same source raised in different laboratories. All but one of the [[testicular]] tumors occurred in the rats from a single supplier. The researchers found that the incidence of tumors in Sprague Dawleys from different suppliers varied as much from each other as from the other strains of rats. The authors of the study "stressed the need for extreme caution in evaluation of [[carcinogen]]icity studies conducted at different laboratories and/or on rats from different sources."<ref>{{Cite journal |date=1973 |issue=5 |volume=50 |publisher=[[Oxford University Press]] (OUP) |pages=1243–1257 |journal=JNCI: Journal of the National Cancer Institute |issn=1460-2105 |id=[[National Cancer Institute]] |last1=Mac Kenzie |first1=William |last2=Garner |first2=F. |title=Comparison of Neoplasms in Six Sources of Rats |doi=10.1093/jnci/50.5.1243| pmid=4712589}}</ref>
During [[Rationing in the United Kingdom|food rationing due to World War II]], British biologists had eaten laboratory rats, creamed.<ref name="Diamond2006">{{cite book |last=Diamond |first=Jared M. |author-link=Jared Diamond |title=Collapse: How Societies Choose to Fail or Succeed |url= https://archive.org/details/collapse00jare |url-access=registration |quote=creamed rat. |date=January 2006 |publisher=[[Penguin Publishing]] |isbn=9780143036555 |pages=[https://archive.org/details/collapse00jare/page/105 105] ''ff.''}}</ref><ref name="Lorey2003">{{cite book |first=David E. |last=Lorey |title=Global Environmental Challenges of the Twenty-first Century: Resources, Consumption, and Sustainable Solutions |url= https://books.google.com/books?id=rptyOXsraDoC&q=creamed+laboratory+rat+creamed+recipes+british+biologist&pg=PA210 |date=2003 |publisher=[[Rowman & Littlefield]] |isbn=9780842050494 |pages=210 ''ff.''}}</ref><ref name="McComb1997">{{cite book |first=David G. |last=McComb |title=Annual Editions: World History |url= https://books.google.com/books?id=DprAlWMgXCsC&q=creamed+laboratory+rat+creamed+recipes+british+biologist |date=1 September 1997 |publisher=[[McGraw-Hill Higher Education]] |isbn=9780697392930 |page=239}}</ref><ref name="Peacock1996">{{cite book |first=Kent Alan |last=Peacock |title=Living with the Earth: An Introduction to Environmental Philosophy |url= https://books.google.com/books?id=myUSAQAAIAAJ&q=creamed+laboratory+rat+creamed+recipes+british+biologist |date=1996 |publisher=[[Harcourt Brace]] Canada |isbn=9780774733779 |page=71}}</ref><ref name="Spears2003">{{cite book |first=Deanne |last=Spears |title=Improving Reading Skills: Contemporary Readings for College Students |url= https://books.google.com/books?id=aUll_BgrqOQC&q=creamed+laboratory+rat+creamed+recipes+british+biologist |date=29 July 2003 |publisher=[[McGraw-Hill]] |isbn=9780072830705 |page=463}}</ref><ref>{{cite book |title=Sovereignty, Colonialism and the Indigenous Nations: A Reader |url= https://books.google.com/books?id=4BaRAAAAMAAJ&q=creamed+laboratory+rat+creamed+recipes+british+biologist |date=2005 |publisher=[[Carolina Academic Press]] |isbn=9780890893333 |page=772}}</ref>
Scientists have also spent time studying the [[thermoregulation]] of the rat's tail in research. The rat's tail works as a variable heat exchanger. The tail's blood flow allows for thermoregulation to take place because it is under control of sympathetic vasoconstrictor nerves.<ref>{{Cite journal |last1=Owens |first1=N. C. |last2=Ootsuka |first2=Y. |last3=Kanosue |first3=K. |last4=McAllen |first4=R. M. |date=2002–2009 |title=Thermoregulatory Control of Sympathetic Fibres Supplying the Rat's Tail |journal=The Journal of Physiology |volume=543 |issue=3 |pages=849–858 |doi=10.1113/jphysiol.2002.023770 |issn=0022-3751 |pmc=2290547 |pmid=12231643}}</ref> [[Vasodilation]] occurs when the tail temperature increases, causing heat loss. [[Vasoconstriction]] occurs when the tail temperature decreases allowing heat to be conserved. Thermoregulation in the rat tail has been used to study metabolism.<ref>{{Cite journal |last1=Škop |first1=Vojtěch |last2=Liu |first2=Naili |last3=Guo |first3=Juen |last4=Gavrilova |first4=Oksana |last5=Reitman |first5=Marc L. |date=1 August 2020 |title=The contribution of the mouse tail to thermoregulation is modest |journal=[[American Journal of Physiology. Endocrinology and Metabolism]] |volume=319 |issue=2 |pages=E438–E446 |doi=10.1152/ajpendo.00133.2020 |issn=0193-1849 |pmc=7473913 |pmid=32691633}}</ref>
==Stocks and strains== {{For|varieties bred as pets|Fancy rat#Varieties}} A "[[Strain (biology)|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 [[genotype]]s are unnecessary or a population with genetic variation is required, and these rats are usually referred to as "stocks" rather than "strains".<ref name=mgi>{{cite web |author=International Committee on Standardized Genetic Nomenclature for Mice / Rat Genome and Nomenclature Committee |title=Rules and Guidelines for Nomenclature of Mouse and Rat Strains |date=January 2016 |url= http://www.informatics.jax.org/mgihome/nomen/strains.shtml#oacc |work=[[Mouse Genome Informatics]] |publisher=[[Jackson Laboratory]] |access-date=5 December 2018}}</ref><ref name="isogenic">{{cite web |title=Outbred Stocks |date=15 February 2019 |url= http://isogenic.info/html/outbred_stocks.html}}</ref>
===Wistar rat=== [[File:Wistar rat.jpg|thumb|right|Wistar rat]] The Wistar rat is an outbred albino rat. This breed was developed at the [[Wistar Institute]] in 1906 for use in biological and medical research, and is notably the first rat developed to serve as a [[model organism]] at a time when laboratories primarily used the [[house mouse]] (''Mus musculus''). More than half of all laboratory rat strains are descended from the original colony established by physiologist [[Henry Herbert Donaldson]], scientific administrator [[Milton J. Greenman]], and genetic researcher/embryologist [[Helen Dean King]].<ref>{{cite journal |last=Clause |first=B. T. |url= http://www.amphilsoc.org/library/mendel/1998.htm |title=The Wistar Institute Archives: Rats (Not Mice) and History |journal=[[Mendel Newsletter]] |date=February 1998 |archive-url= https://web.archive.org/web/20061216054827/http://www.amphilsoc.org/library/mendel/1998.htm |archive-date=16 December 2006}}</ref><ref name="wistar">{{cite web |url= http://www.wistar.org/about_wistar/history.html |title=The Wistar Institute: History |date=2007 |publisher=The [[Wistar Institute]] |access-date=9 November 2008 |url-status=dead |archive-url= https://web.archive.org/web/20081017070234/http://www.wistar.org/about_wistar/history.html |archive-date=17 October 2008}}</ref><ref>{{Cite journal|last=Clause|first=Bonnie Tocher |date=1993 |title=The Wistar rat as a right choice: Establishing mammalian standards and the ideal of a standardized mammal |url= http://link.springer.com/10.1007/BF01061973 |journal=[[Journal of the History of Biology]] |volume=26 |issue=2 |pages=329–349 |doi=10.1007/BF01061973 |pmid=11623164 |s2cid=12428625 |issn=0022-5010|url-access=subscription }}</ref>
The Wistar rat is currently one of the most popular rats used for laboratory research. It is characterized by its wide head, long ears, and a tail length that is always less than its body length. The Sprague Dawley and Long–Evans were developed from Wistars. Wistars are more active than others like Sprague Dawleys. The [[spontaneously hypertensive rat]] and the [[Lewis rat|Lewis]] are other well-known stocks developed from Wistars.
=== Long–Evans rat === The Long–Evans rat is an outbred rat developed by Long and Evans in 1915 by [[Crossbreed|crossbreeding]] 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 research, especially in alcohol research. Long–Evans rats consume alcohol in a much higher rate compared to other strains, thus require less time for these behavioral studies. {{fact|date=March 2023}}
===Sprague Dawley rat=== [[File:SpragueDawleyRat.jpg|thumb|right|Sprague Dawley rat]] The Sprague Dawley is an outbred, multipurpose breed of [[albino rat]] used extensively in medical and nutritional research.<ref>{{cite journal |last1=Drachman |first1=R. H. |last2=Root |first2=R. K. |last3=Wood |first3=W. B. |title=Studies on the effect of experimental nonketotic diabetes mellitus on antibacterial defense. I. Demonstration of a defect in phagocytosis |journal=The Journal of Experimental Medicine |volume=124 |issue=2 |pages=227–240 |date=August 1966 |pmid=4380670 |pmc=2180468 |doi=10.1084/jem.124.2.227}}</ref><ref>{{cite journal |last1=Hsu |first1=C. C. |last2=Lai |first2=S. C. |title=Matrix metalloproteinase-2, -9 and -13 are involved in fibronectin degradation of rat lung granulomatous fibrosis caused by ''Angiostrongylus cantonensis'' |journal=[[International Journal of Experimental Pathology]] |volume=88 |issue=6 |pages=437–443 |date=December 2007 |pmid=18039280 |pmc=2517339 |doi=10.1111/j.1365-2613.2007.00554.x}}</ref><ref>{{cite journal |last1=Horiuchi |first1=N. |last2=Suda |first2=T. |last3=Sasaki |first3=S. |last4=Takahashi |first4=H. |last5=Shimazawa |first5=E. |last6=Ogata |first6=E. |title=Absence of regulatory effects of 1alpha25-dihydroxyvitamin D3 on 25-hydroxyvitamin D metabolism in rats constantly infused with parathyroid hormone |journal=[[Biochemical and Biophysical Research Communications]] |volume=73 |issue=4 |pages=869–875 |date=December 1976 |pmid=15625855 |doi=10.1016/0006-291X(76)90202-3}}</ref><ref>{{cite journal |last1=Sukov |first1=W. |last2=Barth |first2=D. S. |title=Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex |journal=[[Journal of Neurophysiology]] |volume=79 |issue=6 |pages=2875–2884 |date=June 1998 |pmid=9636093 |doi=10.1152/jn.1998.79.6.2875}}</ref> Its main advantage is its calmness and ease of handling.<ref>{{cite web |title=Online Medical Dictionary |archive-url= https://web.archive.org/web/20081202042953/http://cancerweb.ncl.ac.uk/cgi-bin/omd?rats%2C%2Bsprague-dawley |archive-date= 2 December 2008 |url-status=dead |url= http://cancerweb.ncl.ac.uk/cgi-bin/omd?rats,+sprague-dawley |date=12 December 1998 |access-date=15 December 2007}}</ref> This breed of rat was first produced by the Sprague Dawley farms (later to become the [[Harlan (company)|Sprague Dawley Animal Company]]) in [[Madison, Wisconsin]], in 1925. The name was originally hyphenated, although the brand styling today (Sprague Dawley, the trademark used by [[Inotiv]]) is not. The average litter size of the Sprague Dawley rat is 11.0.<ref name="sprague_dawley_rat">{{cite web |title=Sprague Dawley Outbred Rat |url= http://www.harlan.com/products_and_services/research_models_and_services/research_models/sprague_dawley_outbred_rat.hl |publisher=[[Harlan Laboratories]] |access-date=25 October 2012 |archive-url= https://web.archive.org/web/20121026035220/http://www.harlan.com/products_and_services/research_models_and_services/research_models/sprague_dawley_outbred_rat.hl |archive-date=26 October 2012 |url-status=dead}}</ref>
These rats typically have a longer tail in proportion to their body length than Wistars. They were used in the [[Séralini affair]], where the herbicide [[RoundUp]] was claimed to increase the occurrence of tumor in these rats. However, since these rats are known to grow tumors at a high (and very variable) rate, the study was considered flawed in design and its findings unsubstantiated.<ref name=Hayes2014>{{cite journal |last1=Wallace Hayes |first1=A. |title=Editor in Chief of Food and Chemical Toxicology answers questions on retraction |journal=[[Food and Chemical Toxicology]] |volume=65 |pages=394–395 |date=March 2014 |pmid=24407018 |doi=10.1016/j.fct.2014.01.006 |doi-access=free}}</ref>
===Biobreeding rat=== {{Main|Biobreeding rat}} The biobreeding rat (a.k.a. the biobreeding diabetes-prone rat or BBDP rat) is an inbred strain that spontaneously develops autoimmune [[type 1 diabetes]]. Like [[NOD mice]], biobreeding 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.<ref>{{cite journal |last1=Mordes |first1=J. P. |last2=Bortell |first2=R. |last3=Blankenhorn |first3=E. P. |last4=Rossini |first4=A. A. |last5=Greiner |first5=D. L. |title=Rat models of type 1 diabetes: genetics, environment, and autoimmunity |journal=[[ILAR Journal]] |volume=45 |issue=3 |pages=278–291 |date=1 January 2004 |pmid=15229375 |doi=10.1093/ilar.45.3.278 |doi-access=free}}</ref>
===Brattleboro rat=== {{Main|Brattleboro rat}} The Brattleboro rat is a strain that was developed by [[Henry A. Schroeder]] and technician Tim Vinton in [[West Brattleboro]], Vermont, beginning in 1961, for [[Dartmouth Medical School]]. It has a naturally occurring genetic mutation that makes specimens unable to produce the hormone [[vasopressin]], which helps control kidney function. The rats were being raised for laboratory use by Henry Schroeder and technician Tim Vinton, who noticed that the litter of 17 drank and urinated excessively.
===Hairless rat=== {{See also|Fancy rat#Hairless rats|l1=Hairless fancy rat}} Hairless laboratory rats provide researchers with valuable data regarding compromised immune systems and genetic kidney diseases. It is estimated that there are over 25 genes that cause [[Recessive allele|recessive]] hairlessness in laboratory rats.<ref>{{cite journal |last1=Kim |first1=H. |last2=Panteleyev |first2=A. A. |last3=Jahoda |first3=C. A. |last4=Ishii |first4=Y. |last5=Christiano |first5=A. M. |title=Genomic organization and analysis of the hairless gene in four hypotrichotic rat strains |journal=[[Mammalian Genome]] |volume=15 |issue=12 |pages=975–981 |date=December 2004 |pmid=15599556 |doi=10.1007/s00335-004-2383-3 |s2cid=36747187}}</ref> The more common ones are denoted as rnu (Rowett nude), fz (fuzzy), and shn (shorn).
[[File:Nackratte_01.jpg|thumb|A Rowett nude rat]] * Rowett nude rats, first identified in 1953 in Scotland, have no [[thymus]]. The lack of this organ severely compromises their immune system, with infections of the respiratory tract and eyes increasing the most dramatically.<ref name="pmid307688">{{cite journal |last1=Festing |first1=M. F. |last2=May |first2=D. |last3=Connors |first3=T. A. |last4=Lovell |first4=D. |last5=Sparrow |first5=S. |title=An athymic nude mutation in the rat |journal=Nature |volume=274 |issue=5669 |pages=365–366 |date=July 1978 |pmid=307688 |doi=10.1038/274365a0 |bibcode=1978Natur.274..365F |s2cid=4206930}}</ref> * Fuzzy rats were identified in 1976 in a Pennsylvania lab. The leading cause of death among fz/fz rats is ultimately a progressive kidney failure that begins around the age of 1 year.<ref name="pmid513614">{{cite journal |last1=Ferguson |first1=F. G. |last2=Irving |first2=G. W. |last3=Stedham |first3=M. A. |title=Three variations of hairlessness associated with albinism in the laboratory rat |journal=[[Laboratory Animal Science]] |volume=29 |issue=4 |pages=459–464 |date=August 1979 |pmid=513614}}</ref> * Shorn rats were bred from Sprague Dawley rats in Connecticut in 1998.<ref name="pmid9656468">{{cite journal |last1=Moemeka |first1=A. N. |last2=Hildebrandt |first2=A. L. |last3=Radaskiewicz |first3=P. |last4=King |first4=T. R. |title=Shorn (shn): A new mutation causing hypotrichosis in the Norway rat |journal=The Journal of Heredity |volume=89 |issue=3 |pages=257–260 |date=1998 |pmid=9656468 |doi=10.1093/jhered/89.3.257 |doi-access=free}}</ref> They also suffer from severe kidney problems.
===Lewis rat=== The Lewis rat was developed by Margaret Lewis from [[#Wistar rat|Wistar]] stock in the early 1950s. Characteristics include albino coloring, docile behavior, and low fertility.<ref name=CharlesRiver/> The Lewis rat suffers from several spontaneous pathologies: first, they can suffer from high incidences of neoplasms, with the rat's lifespan mainly determined by this. The most common are adenomas of the pituitary and adenomas/adenocarcinomas of the adrenal cortex in both sexes, mammary gland tumors and endometrial carcinomas in females, and C-cell adenomas/adenocarcinomas of the thyroid gland and tumors of the hematopoietic system in males. Second, Lewis rats are prone to develop a spontaneous transplantable lymphatic leukaemia. Lastly, when in advanced age, they sometimes develop spontaneous glomerular sclerosis.<ref name=CharlesRiver/>
Research applications include transplantation research, induced arthritis and inflammation, experimental allergic encephalitis, and STZ-induced diabetes.<ref name=LewisRat>{{cite web |title=Lewis Rat |url= https://www.criver.com/products-services/find-model/lewis-rat?region=3611 |work=CRiver.com |publisher=[[Charles River Laboratories]] |access-date=7 June 2021}}</ref><ref name=CharlesRiver>{{cite web |title=Research Animal Models |url= http://www.criver.com/EN-US/PRODSERV/BYTYPE/RESMODOVER/RESMOD/Pages/LewisRat.aspx |work=CRiver.com |publisher=[[Charles River Laboratories]] |url-status=dead |archive-url= https://web.archive.org/web/20130524145006/http://www.criver.com/EN-US/PRODSERV/BYTYPE/RESMODOVER/RESMOD/Pages/LewisRat.aspx |archive-date=24 May 2013 |date= 2021}}</ref>
===Royal College of Surgeons rat=== [[File:Protective-Effects-of-Human-iPS-Derived-Retinal-Pigment-Epithelium-Cell-Transplantation-in-the-pone.0008152.s003.ogv|thumb|A Royal College of Surgeons rat undergoing visual acuity testing]] The [[Royal College of Surgeons]] rat (or 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 as a mutation in the gene MERTK. This mutation results in defective retinal pigment epithelium phagocytosis of photoreceptor outer segments.<ref> {{cite journal |last1=D'Cruz |first1=P. M. |last2=Yasumura |first2=D. |last3=Weir |first3=J. |last4=Matthes |first4=M. T. |last5=Abderrahim |first5=H. |last6=LaVail |first6=M. M. |last7=Vollrath |first7=D. |title=Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat |journal=[[Human Molecular Genetics]] |volume=9 |issue=4 |pages=645–651 |date=March 2000 |pmid=10699188 |doi=10.1093/hmg/9.4.645 |doi-access=free}}</ref>
===Shaking rat Kawasaki=== <!-- target of redirect --> The shaking rat Kawasaki (SRK) is an [[autosomal recessive]] mutant that has a short deletion in the [[RELN]] (reelin) gene.<ref name="Kikkawa_2003_SRK_Reelin_splicing">{{cite journal |last1=Kikkawa |first1=S. |last2=Yamamoto |first2=T. |last3=Misaki |first3=K. |last4=Ikeda |first4=Y. |last5=Okado |first5=H. |last6=Ogawa |first6=M. |last7=Woodhams |first7=P. L. |last8=Terashima |first8=T. |title=Missplicing resulting from a short deletion in the reelin gene causes reeler-like neuronal disorders in the mutant shaking rat Kawasaki |journal=The Journal of Comparative Neurology |volume=463 |issue=3 |pages=303–315 |date=August 2003 |pmid=12820163 |doi=10.1002/cne.10761 |s2cid=21608635}}</ref> This results in the lowered expression of reelin protein, essential for proper [[Cerebral cortex|cortex]] lamination and [[cerebellum]] development. Its phenotype is similar to the widely researched [[reeler]] mouse. Shaking rat Kawasaki was first described in 1988.<ref name="SRK_Discovery_1988">{{cite journal |last1=Aikawa |first1=H. |last2=Nonaka |first2=I. |last3=Woo |first3=M. |last4=Tsugane |first4=T. |last5=Esaki |first5=K. |title=Shaking rat Kawasaki (SRK): a new neurological mutant rat in the Wistar strain |journal=[[Acta Neuropathologica]] |volume=76 |issue=4 |pages=366–372 |date=1988 |pmid=3176902 |doi=10.1007/bf00686973 |s2cid=5806299}}</ref> This and the Lewis rat are well-known stocks developed from Wistar rats.
===Zucker rat=== [[File:Rat diabetic.jpg|thumb|Zucker rat]] The '''Zucker rat''' was 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 or '''Zucker diabetic fatty rat''' (ZDF rat), which is actually a [[Dominance (genetics)|recessive trait]] (fa/fa) of the [[leptin receptor]], capable of weighing up to {{convert|1|kg|lb}} — more than twice the average weight.<ref name="kurtz">{{cite journal |last1=Kurtz |first1=T. W. |last2=Morris |first2=R. C. |last3=Pershadsingh |first3=H. A. |title=The Zucker fatty rat as a genetic model of obesity and hypertension |journal=Hypertension |volume=13 |issue=6 Pt 2 |pages=896–901 |date=June 1989 |pmid=2786848 |doi=10.1161/01.hyp.13.6.896 |publisher=[[American Heart Association]] |s2cid=109606 |doi-access=free}}</ref><ref name="davis">{{cite journal |last=Davis |first=Amy J. |date=January 1997 |title=The Heart of a Zucker |journal=[[Research PennState]] |volume=18 |issue=1 |url= http://www.rps.psu.edu/jan97/zucker.html |archive-url= https://web.archive.org/web/20020522234402/http://www.rps.psu.edu/jan97/zucker.html |url-status=dead |archive-date=22 May 2002 |access-date=6 December 2008}}</ref><ref>{{cite journal |last1=Takaya |first1=K. |last2=Ogawa |first2=Y. |last3=Isse |first3=N. |last4=Okazaki |first4=T. |last5=Satoh |first5=N. |last6=Masuzaki |first6=H. |last7=Mori |first7=K. |last8=Tamura |first8=N. |last9=Hosoda |first9=K. |last10=Nakao |first10=K. |title=Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats |journal=[[Biochemical and Biophysical Research Communications]] |volume=225 |issue=1 |pages=75–83 |date=August 1996 |pmid=8769097 |doi=10.1006/bbrc.1996.1133 |bibcode=1996BBRC..225...75T }}</ref>
Obese Zucker rats have high levels of [[Hyperlipidemia|lipids]] and [[Hypercholesterolemia|cholesterol]] in their bloodstream, are [[Insulin resistance|resistant to insulin]] without being [[hyperglycemic]], and gain weight from an increase in both the [[Hypertrophy|size]] and [[Hyperplasia|number]] of [[Adipocyte|fat cells]].<ref name="kava">{{cite journal |last1=Kava |first1=R. |last2=Greenwood |first2=M. R. |last3=Johnson |first3=P. R. |date=1990 |title=Zucker (fa/fa) Rat |journal=[[ILAR Journal]] |publisher=[[Institute for Laboratory Animal Research]] (ILAR) |volume=32 |issue=3 |pages=4–8 |doi=10.1093/ilar.32.3.4 |doi-access=free}}</ref> 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.<ref name=davis /><ref name=kava />
===Knockout rats=== {{Main|Knockout rat}} A knockout rat (also spelled ''knock out'' or ''knock-out'') is a [[Genetically modified organism|genetically engineered]] rat with a single gene turned off through a [[Gene trapping|targeted mutation]]. Knockout rats can mimic human diseases, and are important tools for [[Functional genomics|studying gene function]] and for [[drug discovery]] and development. The production of knockout rats became technically feasible in 2008, through work financed by $120 million in funding from the [[National Institutes of Health]] (NIH) via the [[Rat Genome Sequencing Project Consortium]], and work accomplished by the members of the [[Knock Out Rat Consortium]] (KORC). Knockout rat disease models for [[Parkinson's disease]], [[Alzheimer's disease]], [[hypertension]], and [[diabetes]], using [[zinc-finger nuclease]] technology, are being commercialized by [[SAGE Labs]].
== See also == * [[Woolly mouse]] * [[Laboratory mouse]] * [[Animal testing on rodents]] * [[Morris water maze]] * ''[[Rat Genome Database]]''
== References == {{Reflist}}
== Further reading == * {{cite book |editor-first1=Mark A. |editor-last1=Suckow |editor-first2=Steven H. |editor-last2=Weisbroth |editor-first3=Craig L. |editor-last3=Franklin |date=2005 |title=The Laboratory Rat |publisher=[[Academic Press]] |edition=2nd |isbn=0080454321 |url= https://books.google.com/books?id=zJWgc-QBIUYC |via=Google Books}}
== External links == {{Commons category|Lab rats}} * [http://www.nature.com/nature/focus/ratgenome/ "Rat Genome"], ''[[Nature (journal)|Nature]]'' * [http://rgd.mcw.edu/ ''Rat Genome Database''], [[Medical College of Wisconsin]] * [http://www.informatics.jax.org/external/festing/rat/STRAINS.shtml ''Index of Inbred Rat Strains''] database, [[Jacskson Laboratory]] * [https://archive.today/20110726232310/http://www.knockoutrat.org/ratModelSummary.php ''Rat Model Summary''] database, [[Knock Out Rat Consortium]] (archived copy)
{{Model Organisms}} {{Authority control}}
[[Category:Laboratory rats| ]] [[Category:Animal models]] [[Category:Articles containing video clips]]