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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
267:, 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 137:
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.
1326:"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" 1217:
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
2045: 230:(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. 2128: 1918: 77:. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for 391:"Effective Utilization and Appropriate Selection of Genetically Engineered Mouse Models for Translational Integration of Mouse and Human Trials" 1219:"Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse" 158:
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
753:"The origins of oncomice: a history of the first transgenic mice genetically engineered to develop cancer" 1526: 845: 272: 187: 1140:
Elisabeth R. Barton-Davis; Daria I. Shoturma; Antonio Musaro; Nadia Rosenthal; H. Lee Sweeney (1998).
701:"Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs" 2065: 1840: 1606: 1467: 1153: 1098: 805: 657: 614: 508: 175: 118: 648:
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).
295:. Another mouse has had a gene altered that is involved in 246:, which glows green under blue light. The central mouse is 214:. For example, genetically modified mice may be born with 226:
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).
1200:"Genetically engineered super mouse stuns scientists" 982:"Background: Cloned and Genetically Modified Animals" 389:
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 307:blocked or removed in a study involving 340: 154:, a technique developed and refined by 908:Yong KS, Her Z, Chen Q (August 2018). 843: 1059: 1057: 1055: 1007: 1005: 1003: 7: 275:have provided good models for human 2076:Genetic use restriction technology 561:American Journal of Human Genetics 67:(PDXs), GEMMs are the most common 41:genetically engineered mouse model 25: 1294:10.1111/j.1601-183X.2008.00438.x 495:Jaenisch, R.; Mintz, B. (1974). 2094:Cartagena Protocol on Biosafety 1331:Chemical Research in Toxicology 1224:Journal of Biological Chemistry 1: 1856:Somatic cell nuclear transfer 446:Nature Reviews Drug Discovery 367:10.1158/0008-5472.CAN-11-2786 133:injected purified DNA into a 958:"Mouse strain C57BL/6-Mcph1" 879:10.1016/0092-8674(87)90646-5 717:10.1016/0092-8674(81)90376-7 395:Cold Spring Harbor Protocols 289:insulin-like growth factor I 222:into them in order to study 242:Transgenic mice expressing 59:altered through the use of 2246: 798:Proc. Natl. Acad. Sci. USA 574:10.1016/j.ajhg.2013.05.012 291:(IGF-I) in differentiated 271:and knockout mice lacking 127:University of Pennsylvania 65:patient-derived xenografts 37:genetically modified mouse 2179: 1914:Genetically modified food 1280:Genes, Brain and Behavior 926:10.1007/s00005-018-0506-x 556:"Frank Ruddle (1929–2013" 303:). Another mouse had the 244:green fluorescent protein 182:containing DNA sequences 18:Genetically modified mice 1167:10.1073/pnas.95.26.15603 135:single-cell mouse embryo 131:University of Washington 819:10.1073/pnas.77.12.7380 627:10.1126/science.6272397 273:tumor suppressing genes 216:human leukocyte antigen 1238:10.1074/jbc.M706127200 962:The Jackson Laboratory 522:10.1073/pnas.71.4.1250 251: 32: 2225:1974 in biotechnology 1527:Roundup ready soybean 501:Proc. Natl. Acad. Sci 408:10.1101/pdb.top078774 241: 174:, involves modifying 30: 2066:Reverse transfection 1841:Genetic transduction 988:on November 23, 2016 279:. Hundreds of these 176:embryonic stem cells 152:pronuclear injection 2230:Genetic engineering 2056:Genetics in fiction 1988:Genetic enhancement 1790:Hepatitis B vaccine 1420:Genetic engineering 1231:(45): 32844–32855. 1206:. November 3, 2007. 1158:1998PNAS...9515603B 1152:(26): 15603–15607. 1103:1997Natur.387...83M 810:1980PNAS...77.7380G 770:10.1101/gad.1583307 711:(1 Pt 2): 223–231. 662:1981Natur.294...92C 619:1981Sci...214.1244G 513:1974PNAS...71.1250J 301:Metabolic supermice 212:human-animal hybrid 61:genetic engineering 55:) that has had its 2166:Stem cell research 1785:Ice-minus bacteria 297:glucose metabolism 252: 33: 2207: 2206: 2171:Synthetic biology 2061:Human enhancement 2051:Genetic pollution 2027: 2026: 1895: 1894: 1803: 1802: 1766: 1765: 1660: 1659: 1344:10.1021/tx200143x 804:(12): 7380–7384. 763:(18): 2258–2270. 401:(11): 1006–1011. 360:(11): 2695–2700. 228:hepatitis C virus 220:white blood cells 156:Ralph L. Brinster 123:Ralph L. Brinster 16:(Redirected from 2237: 1944:Dow AgroSciences 1904: 1814: 1671: 1446: 1437: 1413: 1406: 1399: 1390: 1366: 1365: 1355: 1321: 1315: 1314: 1296: 1267: 1261: 1260: 1250: 1240: 1214: 1208: 1207: 1196: 1190: 1189: 1179: 1169: 1137: 1131: 1130: 1111:10.1038/387083a0 1086: 1080: 1079: 1077: 1076: 1061: 1050: 1049: 1042: 1036: 1035: 1019: 1016:Transgenic Mouse 1009: 998: 997: 995: 993: 978: 972: 971: 969: 968: 954: 948: 947: 937: 905: 899: 898: 862: 856: 855: 849: 841: 831: 821: 789: 783: 782: 772: 748: 739: 738: 728: 696: 690: 689: 670:10.1038/294092a0 645: 639: 638: 613:(4526): 1244–6. 602: 596: 595: 585: 551: 545: 544: 534: 524: 507:(4): 1250–1254. 492: 486: 485: 437: 431: 430: 420: 410: 386: 380: 379: 369: 345: 83:pharmacodynamics 79:drug development 21: 2245: 2244: 2240: 2239: 2238: 2236: 2235: 2234: 2210: 2209: 2208: 2203: 2175: 2144: 2098: 2080: 2033: 2023: 1997: 1993:Genetic testing 1975: 1965: 1891: 1877:Recombinant DNA 1865: 1836:Electroporation 1799: 1795:Oncolytic virus 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Index

Genetically modified mice

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

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