Genetically modified mammal

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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[edit]

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]

Genetically modified mice[edit]

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.

Genetically modified rats[edit]

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

Genetically modified goats[edit]

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]

Genetically modified pigs[edit]

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.

Genetically modified cattle[edit]

Herman the Bull was in 1991 the first genetically modified or transgenic bovine in the world.[20][21] The announcement of Herman's creation caused an ethical storm.[22]

Genetically modified dogs[edit]

Ruppy (short for Ruby Puppy) was in 2009 the world's first Genetically modified dog.[23] A cloned beagle, Ruppy and four other beagles produced a fluorescent protein that glowed red upon excitation with ultraviolet light.[24] It was hoped to use this procedure to investigate the effect of the hormone oestrogen on fertility.[24]

Genetically modified primates[edit]

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 is hoped that this will aid research into human diseases that cannot be studied in mice, for example Huntington's disease and strokes.[25][26]

Genetically modified cats[edit]

In 2011 a Japanese-American Team created genetically modified green-fluorescent cats in order to find therapies for HIV/AIDS and other diseases[27] as Feline immunodeficiency virus (FIV) is related to HIV.[28]

References[edit]

  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.  edit
  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.  edit
  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.  edit
  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. 
  8. ^ Highfield, Roger (2007-11-02). "Genetically engineered 'mighty mouse' is the rodent Lance Armstrong". London: Telegraph. 
  9. ^ Abbott A: Laboratory animals: the Renaissance rat. Nature 2004, 428:464-466.
  10. ^ Zhou Q, Renard JP, Le Friec G, Brochard V, Beaujean N, Cherifi Y, Fraichard A, Cozzi J: Generation of fertile cloned rats by regulating oocyte activation. Science 2003, 302:1179.
  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: Transposon-tagged mutagenesis in the rat. Nat Methods 2007, 4:131-133.
  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 & Cananda, 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 AFP, Retrieved 31 August 2012
  17. ^ a b Randall S. et al (2008) Genetically Modified Pigs for Medicine and Agriculture Biotechnology and Genetic Engineering Reviews - Vol. 25, 245-266, Retrieved 31 August 2012
  18. ^ Staff (2006) NTU produces green fluorescent pigs for medical research Taiwan Central News Agency, Retrieved 31 August 2012
  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. doi:10.1117/1.3241985. PMID 19895119.  edit
  20. ^ Naturalis (2008). Herman the Bull stabled in Naturalis. Accessed on 3 January 2009 from www.naturalis.nl/naturalis.en/naturalis.en/i000968.html.
  21. ^ De Boer, H.A. et al. (1991): Generation of transgenic dairy cattle using 'in vitro' embryo production, Biotechnology (9): 844-7
  22. ^ 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
  23. ^ "Fluorescent puppy is world's first transgenic dog". New Scientist. 23 April 2009. 
  24. ^ a b "World's First Transgenic Dog-Fluorescent 'Ruppy'". 
  25. ^ Palmer, Jason (27 May 2009). "Glowing monkeys 'to aid research'". BBC News. Retrieved 2009-05-28. 
  26. ^ 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. 
  27. ^ 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. PMID 21909101. 
  28. ^ Staff (3 April 2012) Biology of HIV National Institute of Allergy and Infectious Diseases, Retrieved 31 August 2012