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Genetically modified mammal

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Part of a series on
Genetic engineering
 
Genetically modified organisms
History and regulation
Process
Applications
Controversies

Genetically modified mammals are mammals that have been genetically engineered. They are an important category of genetically modified organisms. The majority of research involving genetically modified mammals involves mice with attempts to produce knockout animals in other mammalian species limited by the inability to derive and stably culture embryonic stem cells.[1]

Usage

The majority of genetically modified mammals are used in research to investigate changes in phenotype when specific genes are altered. This can be used to discover the function of an unknown gene, any genetic interactions that occur or where the gene is expressed. Genetic modification can also produce mammals that are susceptible to certain compounds or stresses for testing in biomedical research.[2] Some genetically modified mammals are used as models of human diseases and potential treatments and cures can first be tested on them. Other mammals have been engineered with the aim of potentially increasing their use to medicine and industry. These possibilities include pigs expressing human antigens aiming to increasing the success of xenotransplantation[3] to lactating mammals expressing useful proteins in their milk.[4]

Mice

Main article: Genetically modified mouse

Genetically modified mice are often used to study cellular and tissue-specific responses to disease (cf knockout mouse). This is possible since mice can be created with the same mutations that occur in human genetic disorders, the production of the human disease in these mice then allows treatments to be tested.[5]

The oncomouse is a type of laboratory mouse that has been genetically modified developed by Philip Leder and Timothy A. Stewart of Harvard University to carry a specific gene called an activated oncogene.[6]

Metabolic supermice are the creation of a team of American scientists led by Richard Hanson, professor of biochemistry at Case Western Reserve University at Cleveland, Ohio.[7][8] The aim of the research was to gain a greater understanding of the PEPCK-C enzyme, which is present mainly in the liver and kidneys.

Rats

A knockout rat is a rat with a single gene disruption used for academic and pharmaceutical research.[9][10][11][12]

Goats

BioSteel is a trademark name for a high-strength based fiber material made of the recombinant spider silk-like protein extracted from the milk of transgenic goats, made by Nexia Biotechnologies. The company has successfully generated distinct lines of goats that produce in their milk recombinant versions of either the MaSpI or MaSpII dragline silk proteins, respectively. Nexia Biotechnologies, however, went bankrupt and is no longer company.[13]

Pigs

The enviropig is the trademark for a genetically modified line of Yorkshire pigs with the capability to digest plant phosphorus more efficiently than ordinary unmodified pigs that was developed at the University of Guelph.[14] Enviropigs produce the enzyme phytase in the salivary glands that is secreted in the saliva.

In 2006 the scientists from National Taiwan University's Department of Animal Science and Technology managed to breed three green-glowing pigs using green fluorescent protein.[15] Fluorescent pigs can be used to study human organ transplants,[16] regenerating ocular photoreceptor cells,[17] neuronal cells in the brain,[17] regenerative medicine via stem cells,[18] tissue engineering,[19] and other diseases.

In 2015, researchers at the Beijing Genomics Institute used transcription activator-like effector nucleases to create a miniature version of the Bama breed of pigs, and offered them for sale to consumers.[20]

In 2017 scientists at the Roslin Institute of the University of Edinburgh, reported they had bred pigs with a modified CD163 gene. These pigs were completely resistant to Porcine Reproductive and Respiratory Syndrome, a disease that causes major losses in the world-wide pig industry.[21]

Cattle

Herman the Bull was in 1991 the first genetically modified or transgenic bovine in the world.[22][23] The announcement of Herman's creation caused an ethical storm.[24]

Dogs

Ruppy (short for Ruby Puppy) was in 2009 the world's first Genetically modified dog.[25] A cloned beagle, Ruppy and four other beagles produced a fluorescent protein that glowed red upon excitation with ultraviolet light.[26] It was hoped to use this procedure to investigate the effect of the hormone oestrogen on fertility.[26]

A team in China reported in 2015 that they had genetically engineered beagles to have twice the normal muscle mass, inserting a natural myostatin gene mutation taken from whippets.[27][28]

Primates

In 2009 scientists in Japan announced that they had successfully transferred a gene into a primate species (marmosets) and produced a stable line of breeding transgenic primates for the first time. It was hoped that this would aid research into human diseases that cannot be studied in mice, for example Huntington's disease, strokes,[29][30] Alzheimer's disease and schizophrenia.[31]

Cats

In 2011 a Japanese-American Team created genetically modified green-fluorescent cats in order to find therapies for HIV/AIDS and other diseases[32] as Feline immunodeficiency virus (FIV) is related to HIV.[33]

References

  1. ^ Golding, M.; Long, C.; Carmell, M.; Hannon, G.; Westhusin, M. (2006). "Suppression of prion protein in livestock by RNA interference". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5285–5290. Bibcode:2006PNAS..103.5285G. doi:10.1073/pnas.0600813103. PMC 1459347. PMID 16567624.
  2. ^ Sathasivam K, Hobbs C, Mangiarini L, et al. (June 1999). "Transgenic models of Huntington's disease". Philos. Trans. R. Soc. Lond. B Biol. Sci. 354 (1386): 963–9. doi:10.1098/rstb.1999.0447. PMC 1692600. PMID 10434294.
  3. ^ Edge, A.; Gosse, M.; Dinsmore, J. (1998). "Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation". Cell Transplantation. 7 (6): 525–539. doi:10.1016/S0963-6897(98)00043-8. PMID 9853581.
  4. ^ Vollrath, F.; Knight, D. (2001). "Liquid crystalline spinning of spider silk". Nature. 410 (6828): 541–548. Bibcode:2001Natur.410..541V. doi:10.1038/35069000. PMID 11279484. S2CID 205015549.
  5. ^ Wagner J, Thiele F, Ganten D (May 1995). "Transgenic animals as models for human disease". Clin. Exp. Hypertens. 17 (4): 593–605. doi:10.3109/10641969509037410. PMID 7795575.
  6. ^ European Patent Register entry for European patent no. 0169672, under "Inventor(s)". Consulted on February 22, 2008.
  7. ^ Connor, Steve (2007-11-02). "The mouse that shook the world". London: The Independent. Archived from the original on 2008-05-16. Retrieved 2009-11-26.
  8. ^ Highfield, Roger (2007-11-02). "Genetically engineered 'mighty mouse' is the rodent Lance Armstrong". London: Telegraph.
  9. ^ Abbott, A (2004). "Laboratory animals: the Renaissance rat". Nature. 428 (6982): 464–466. Bibcode:2004Natur.428..464A. doi:10.1038/428464a. PMID 15057803. S2CID 11473955.
  10. ^ Zhou, Q; Renard, JP; Le Friec, G; Brochard, V; Beaujean, N; Cherifi, Y; Fraichard, A; Cozzi, J (2003). "Generation of fertile cloned rats by regulating oocyte activation" (PDF). Science. 302 (5648): 1179. doi:10.1126/science.1088313. PMID 14512506. S2CID 38107285.
  11. ^ Justice MJ, Noveroske JK, Weber JS, Zheng B, Bradley A: Mouse ENU mutagenesis" Hum Mol Genet 1999; 8:1955-1963.
  12. ^ Kitada, K; Ishishita, S; Tosaka, K; Takahashi, R; Ueda, M; Keng, VW; Horie, K; Takeda, J (2007). "Transposon-tagged mutagenesis in the rat". Nat Methods. 4 (2): 131–133. doi:10.1038/nmeth1002. PMID 17220894. S2CID 7525987.
  13. ^ Biopolymer, Volume 8 Polyamides and Complex Proteinaceous Materials II, edited by S.R. Fahnestock & A. Steinbuchel, 2003 Wiley-VCH Verlag, pages 97-117 ISBN 978-3-527-30223-9
  14. ^ Cooke, Jeremy GM pigs: Green ham with your eggs? BBC News US & Canada, 4 January 2011, retrieved 5 January 2011
  15. ^ Hogg, Chris (12 January 2006) Taiwan breeds green-glowing pigs BBC News, Retrieved 1 September 2012
  16. ^ Staff (8 January 2008) Fluorescent Chinese pig passes on trait to offspring Archived 2012-07-25 at the Wayback Machine AFP, Retrieved 31 August 2012
  17. ^ a b Randall, S.; et al. (2008). e. Harding, Stephen; p. Tombs, Michael (eds.). "Genetically Modified Pigs for Medicine and Agriculture" (PDF). Biotechnology and Genetic Engineering Reviews. 25: 245–266. doi:10.7313/upo9781904761679.011. ISBN 9781904761679. PMID 21412358. Archived from the original (PDF) on 2014-03-26.
  18. ^ "Gene Transfer Breakthroughs at NTU: Advanced Biotechnology Creates Fluorescent Green Transgenic Fish and Pigs that Possess Ornamental and Research Value" (PDF). National Taiwan University Newsletter. 3: 14–15. December 2007. Retrieved 19 October 2015.
  19. ^ Kawarasaki, T.; Uchiyama, K.; Hirao, A.; Azuma, S.; Otake, M.; Shibata, M.; Tsuchiya, S.; Enosawa, S.; Takeuchi, K.; Konno, K.; Hakamata, Y.; Yoshino, H.; Wakai, T.; Ookawara, S.; Tanaka, H.; Kobayashi, E.; Murakami, T. (2009). "Profile of new green fluorescent protein transgenic Jinhua pigs as an imaging source". Journal of Biomedical Optics. 14 (5): 054017. Bibcode:2009JBO....14e4017K. doi:10.1117/1.3241985. PMID 19895119.
  20. ^ Editor, Robin Mckie Science (2015-10-03). "£1,000 for a micro-pig. Chinese lab sells genetically modified pets". The Guardian. {{cite news}}: |last1= has generic name (help)
  21. ^ "Super pigs created by scientists that are immune to 'mystery swine disease'". Express. 2017-02-23. Retrieved 2017-02-24.
  22. ^ Naturalis (2008). Herman the Bull stabled in Naturalis. Accessed on 3 January 2009 from www.naturalis.nl/naturalis.en/naturalis.en/i000968.html.
  23. ^ De Boer, H.A.; et al. (1991). "Generation of transgenic dairy cattle using 'in vitro' embryo production". Biotechnology. 9 (9): 844–7. doi:10.1038/nbt0991-844. PMID 1367358. S2CID 20074481.
  24. ^ Expatica News (2 April 2004). Herman the bull heads to greener pastures. Accessed on 3 January 2009 from http://www.expatica.com/nl/news/local_news/herman-the-bull-heads-to-greener-pastures--6273.html
  25. ^ "Fluorescent puppy is world's first transgenic dog". New Scientist. 23 April 2009.
  26. ^ a b "World's First Transgenic Dog-Fluorescent 'Ruppy'". 2009-04-24.
  27. ^ Will Heilpern (28 October 2015). "Super-strong, genetically-engineered dogs -- Could they cure Parkinson's disease?". CNN.
  28. ^ Antonio Regalado (19 October 2015). "First Gene-Edited Dogs Reported in China". Technology Review.
  29. ^ Palmer, Jason (27 May 2009). "Glowing monkeys 'to aid research'". BBC News. Retrieved 2009-05-28.
  30. ^ Cyranoski, D (2009). "Newly created transgenic primate may become an alternative disease model to rhesus macaques". Nature. 459 (7246): 492. doi:10.1038/459492a. PMID 19478751.
  31. ^ Okano, Hideyuki; Partha, Mitra (April 2015). "Brain-mapping projects using the common marmoset". Neuroscience Research. 93: 3–7. doi:10.1016/j.neures.2014.08.014. PMID 25264372.
  32. ^ Wongsrikeao P, Saenz D, Rinkoski T, Otoi T, Poeschla E (2011). "Antiviral restriction factor transgenesis in the domestic cat". Nature Methods. 8 (10): 853–9. doi:10.1038/nmeth.1703. PMC 4006694. PMID 21909101.
  33. ^ Staff (3 April 2012) Biology of HIV Archived April 11, 2014, at the Wayback Machine National Institute of Allergy and Infectious Diseases, Retrieved 31 August 2012
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