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Genetically modified mouse

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are similar to that of a human and they carry virtually all the same genes that operate in humans. They also have advantages over other mammals, in regards to research, in that they are available in hundreds of genetically homogeneous strains. Also, due to their size, they can be kept and housed in
256:, where the activity of a single (or in some cases multiple) genes are removed. They have been used to study and model obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging, temperature and pain reception, and Parkinson disease. Transgenic mice generated to carry cloned 126:
utilizing techniques developed by Brinster in the 1960s and 1970s, showing transmission of the genetic material to subsequent generations for the first time. During the 1980s, Palmiter and Brinster developed and led the field of transgenesis, refining methods of
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have been developed covering a wide range of cancers affecting most organs of the body and they are being refined to become more representative of human cancer. The disease symptoms and potential drugs or treatments can be tested against these mouse models.
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Great care should be taken when deciding how to use genetically modified mice in research. Even basic issues like choosing the correct "wild-type" control mouse to use for comparison are sometimes overlooked.
1315:"Mispairing C57BL/6 Substrains of Genetically Engineered Mice and Wild-Type Controls Can Lead to Confounding Results as It Did in Studies of JNK2 in Acetaminophen and Concanavalin A Liver Injury" 1206:
Hakimi P, Yang J, Casadesus G, Massillon D, Tolentino-Silva F, Nye C, Cabrera M, Hagen D, Utter C, Baghdy Y, Johnson DH, Wilson DL, Kirwan JP, Kalhan SC, Hanson RW (2007).
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techniques. Genetically modified mice are commonly used for research or as animal models of human diseases and are also used for research on genes. Together with
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the target gene, although increasingly more subtle and complex genetic manipulation can occur (e.g. humanisation of a specific protein, or only changing single
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Genetically modified mice are used extensively in research as models of human disease. Mice are a useful model for genetic manipulation and research, as their
2034: 219:(HCV) peptides that bind to HLA, and that can be recognized by the human immune system, thereby potentially being targets for future vaccines against HCV. 2117: 1907: 66:. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for 380:"Effective Utilization and Appropriate Selection of Genetically Engineered Mouse Models for Translational Integration of Mouse and Human Trials" 1208:"Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse" 147:
in the 1960s and 1970s, into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. This method creates a
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modification and using these techniques to elucidate the activity and function of genes in a way not possible before their unique approach.
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The genetically modified mouse in which a gene affecting hair growth has been knocked out (left) shown next to a normal lab mouse
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McPherron, A.; Lawler, A.; Lee, S. (1997). "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member".
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to their offspring, and the impact and applicability of this experiment were, therefore, limited. In 1981 the laboratories of
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and runs faster, lives longer, is more sexually active and eats more without getting fatter than the average mouse (see
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Gordon, J.; Ruddle, F. (1981). "Integration and stable germ line transmission of genes injected into mouse pronuclei".
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Thomas KR, Capecchi MR (1987). "Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells".
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A mouse has been genetically engineered to have increased muscle growth and strength by overexpressing the
742:"The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer" 1515: 834: 261: 176: 1129:
Elisabeth R. Barton-Davis; Daria I. Shoturma; Antonio Musaro; Nadia Rosenthal; H. Lee Sweeney (1998).
690:"Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs" 2054: 1829: 1595: 1456: 1142: 1087: 794: 646: 603: 497: 164: 107: 637:
Costantini, F.; Lacy, E. (1981). "Introduction of a rabbit β-globin gene into the mouse germ line".
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and showing that the inserted genes were present in every cell. However, the mice did not pass the
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There are two basic technical approaches to produce genetically modified mice. The first involves
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created the first genetically modified animal by inserting a DNA virus into an early-stage mouse
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mouse and is used to insert new genetic information into the mouse genome or to over-express
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large numbers, reducing the cost of research and experiments. The most common type is the
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Gordon, J.W., Scangos, G.A, Plotkin, D.J., Barbosa, J.A. and Ruddle F.H. (1980).
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with the genomic DNA are selected for and they are then injected into the mice
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genes in order to provide a more realistic environment when introducing human
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Brinster R, Chen HY, Trumbauer M, Senear AW, Warren R, Palmiter RD (1981).
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can also be created by direct addition of human genes, thereby creating a
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Mammalian Genetics Unit Harwell: Mouse models for human disease
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Douglas Hanahan; Erwin F. Wagner; Richard D. Palmiter (2007).
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Sharpless, Norman E.; DePinho, Ronald A. (September 2006).
284:. Another mouse has had a gene altered that is involved in 235:, which glows green under blue light. The central mouse is 203:. For example, genetically modified mice may be born with 215:
responses. One such application is the identification of
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Mohammed Bourdi; John S. Davies; Lance R. Pohl (2011).
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Singh, M.; Murriel, C. L.; Johnson, L. (16 May 2012).
1189:"Genetically engineered super mouse stuns scientists" 971:"Background: Cloned and Genetically Modified Animals" 378:
Abate-Shen, C.; Pandolfi, P. P. (30 September 2013).
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List of varieties of genetically modified maize/corn
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The second approach, pioneered by 296:blocked or removed in a study involving 329: 143:, a technique developed and refined by 897:Yong KS, Her Z, Chen Q (August 2018). 832: 1048: 1046: 1044: 996: 994: 992: 7: 264:have provided good models for human 2065:Genetic use restriction technology 550:American Journal of Human Genetics 56:(PDXs), GEMMs are the most common 30:genetically engineered mouse model 14: 1283:10.1111/j.1601-183X.2008.00438.x 484:Jaenisch, R.; Mintz, B. (1974). 2083:Cartagena Protocol on Biosafety 1320:Chemical Research in Toxicology 1213:Journal of Biological Chemistry 1: 1845:Somatic cell nuclear transfer 435:Nature Reviews Drug Discovery 356:10.1158/0008-5472.CAN-11-2786 122:injected purified DNA into a 947:"Mouse strain C57BL/6-Mcph1" 868:10.1016/0092-8674(87)90646-5 706:10.1016/0092-8674(81)90376-7 384:Cold Spring Harbor Protocols 278:insulin-like growth factor I 211:into them in order to study 231:Transgenic mice expressing 48:altered through the use of 2235: 787:Proc. Natl. Acad. Sci. USA 563:10.1016/j.ajhg.2013.05.012 280:(IGF-I) in differentiated 260:and knockout mice lacking 116:University of Pennsylvania 54:patient-derived xenografts 26:genetically modified mouse 2168: 1903:Genetically modified food 1269:Genes, Brain and Behavior 915:10.1007/s00005-018-0506-x 545:"Frank Ruddle (1929–2013" 292:). Another mouse had the 233:green fluorescent protein 171:containing DNA sequences 1156:10.1073/pnas.95.26.15603 124:single-cell mouse embryo 120:University of Washington 808:10.1073/pnas.77.12.7380 616:10.1126/science.6272397 262:tumor suppressing genes 205:human leukocyte antigen 1227:10.1074/jbc.M706127200 951:The Jackson Laboratory 511:10.1073/pnas.71.4.1250 240: 21: 2214:1974 in biotechnology 1516:Roundup ready soybean 490:Proc. Natl. Acad. Sci 397:10.1101/pdb.top078774 230: 163:, involves modifying 19: 2055:Reverse transfection 1830:Genetic transduction 977:on November 23, 2016 268:. Hundreds of these 165:embryonic stem cells 141:pronuclear injection 2219:Genetic engineering 2045:Genetics in fiction 1977:Genetic enhancement 1779:Hepatitis B vaccine 1409:Genetic engineering 1220:(45): 32844–32855. 1195:. November 3, 2007. 1147:1998PNAS...9515603B 1141:(26): 15603–15607. 1092:1997Natur.387...83M 799:1980PNAS...77.7380G 759:10.1101/gad.1583307 700:(1 Pt 2): 223–231. 651:1981Natur.294...92C 608:1981Sci...214.1244G 502:1974PNAS...71.1250J 290:Metabolic supermice 201:human-animal hybrid 50:genetic engineering 44:) that has had its 2155:Stem cell research 1774:Ice-minus bacteria 286:glucose metabolism 241: 22: 2196: 2195: 2160:Synthetic biology 2050:Human enhancement 2040:Genetic pollution 2016: 2015: 1884: 1883: 1792: 1791: 1755: 1754: 1649: 1648: 1333:10.1021/tx200143x 793:(12): 7380–7384. 752:(18): 2258–2270. 390:(11): 1006–1011. 349:(11): 2695–2700. 217:hepatitis C virus 209:white blood cells 145:Ralph L. Brinster 112:Ralph L. 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Index


mouse
genome
genetic engineering
patient-derived xenografts
in vivo
cancer research
drug development
pharmacodynamics
Beatrice Mintz
Rudolf Jaenisch
embryo
transgene
Frank Ruddle
Yale University
Oxford
Ralph L. Brinster
University of Pennsylvania
University of Washington
single-cell mouse embryo
germline
pronuclear injection
Ralph L. Brinster
transgenic
endogenous
Oliver Smithies
Mario Capecchi
embryonic stem cells
DNA construct
homologous

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