Genetically modified mammal explained

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

See 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. Prior to its bankruptcy, the company successfully generated distinct lines of goats that produced recombinant versions of either the MaSpI or MaSpII dragline silk proteins, respectively, in their milk.[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, in collaboration with Genus, 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

In 1991, Herman the Bull was the first genetically modified or transgenic bovine in the world.[22] [23] The announcement of Herman's creation generated considerable controversy.[24]

In 2016 Jayne Raper and her team announced the first trypanotolerant transgenic cow in the world. This team, spanning the International Livestock Research Institute, Scotland's Rural College, the Roslin Institute's Centre for Tropical Livestock Genetics and Health, and the City University of New York, announced that a Kenyan Boran bull had been born and had already successfully had two children. Tumaini  - named for the Swahili word for "hope"  - had been given a trypanolytic factor from a baboon via CRISPR/Cas9.[25] [26]

Dogs

Ruppy (short for Ruby Puppy) was in 2009 the world's first genetically modified dog.[27] A cloned beagle, Ruppy and four other beagles produced a fluorescent protein that glowed red upon excitation with ultraviolet light.[28] It was hoped to use this procedure to investigate the effect of the hormone estrogen on fertility.[28]

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.[29] [30]

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,[31] [32] Alzheimer's disease and schizophrenia.[33]

Cats

In 2011 a Japanese-American Team created genetically modified green-fluorescent cats in order to study HIV/AIDS and other diseases[34] as Feline immunodeficiency virus (FIV) is related to HIV.[35]

Notes and References

  1. 14. 103. Proceedings of the National Academy of Sciences of the United States of America. 5285–5290. 2006. 10.1073/pnas.0600813103. 1459347. 16567624. Suppression of prion protein in livestock by RNA interference . M. . C.. Long . M.. Carmell . M.. Westhusin . G.. Hannon. Golding. 2006PNAS..103.5285G . free.
  2. Sathasivam K, Hobbs C, Mangiarini L, etal . Transgenic models of Huntington's disease . . 354 . 1386 . 963–9 . June 1999 . 10434294 . 1692600 . 10.1098/rstb.1999.0447 .
  3. 6. 7. 525–539. 1998. 10.1016/S0963-6897(98)00043-8. 9853581. Cell Transplantation. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Gosse . A. . M.. Dinsmore . J.. Edge.
  4. 541–548. 6828. 2001. 11279484. 10.1038/35069000. 410. Nature . F.. Knight . D.. Liquid crystalline spinning of spider silk. Vollrath. 2001Natur.410..541V . 205015549.
  5. Wagner J, Thiele F, Ganten D . Transgenic animals as models for human disease . Clin. Exp. Hypertens. . 17 . 4 . 593–605 . May 1995 . 7795575 . 10.3109/10641969509037410.
  6. , under "Inventor(s)". Consulted on February 22, 2008.
  7. News: The mouse that shook the world. Steve. Connor. The Independent. 2007-11-02. London. 2009-11-26. https://web.archive.org/web/20080516055820/http://news.independent.co.uk/sci_tech/article3121157.ece. 2008-05-16. dead.
  8. News: Genetically engineered 'mighty mouse' is the rodent Lance Armstrong. https://web.archive.org/web/20071105035802/http://www.telegraph.co.uk/earth/main.jhtml?view=DETAILS&grid=&xml=/earth/2007/11/01/scimice101.xml. dead. 2007-11-05. Roger. Highfield. Telegraph. 2007-11-02. London.
  9. Abbott . A . 2004 . Laboratory animals: the Renaissance rat . Nature . 428 . 6982. 464–466 . 10.1038/428464a. 15057803 . 2004Natur.428..464A . 11473955 . free .
  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 . Science . 302. 5648 . 1179 . 10.1126/science.1088313 . 14512506. 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 . 10.1038/nmeth1002. 17220894 . 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
  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 AFP, Retrieved 31 August 2012
  17. Randall . S. . Michael . p. Tombs . Stephen . e. Harding . etal . 2008 . Genetically Modified Pigs for Medicine and Agriculture . Biotechnology and Genetic Engineering Reviews . 25 . 245–266 . 10.7313/upo9781904761679.011 . 21412358 . 9781904761679 . dead . https://web.archive.org/web/20140326024622/http://www.nottingham.ac.uk/ncmh/BGER/pdf/volume_25/11-Prather.pdf . 2014-03-26 .
  18. Gene Transfer Breakthroughs at NTU: Advanced Biotechnology Creates Fluorescent Green Transgenic Fish and Pigs that Possess Ornamental and Research Value. National Taiwan University Newsletter. December 2007. 3. 14–15. 19 October 2015.
  19. Kawarasaki . T. . Uchiyama . K. . Hirao . A. . Azuma . S. . Otake . M. . Shibata . M. . Tsuchiya . S. . Enosawa . S. . Takeuchi . K. . Konno . 10.1117/1.3241985 . K. . Hakamata . Y. . Yoshino . H. . Wakai . T. . Ookawara . S. . Tanaka . H. . Kobayashi . E. . Murakami . T. . Profile of new green fluorescent protein transgenic Jinhua pigs as an imaging source . Journal of Biomedical Optics . 14 . 5 . 054017 . 2009 . 19895119 . 2009JBO....14e4017K . 206427813 . free .
  20. News: £1,000 for a micro-pig. Chinese lab sells genetically modified pets. The Guardian. 2015-10-03. Editor. Robin Mckie Science.
  21. News: Super pigs created by scientists that are immune to 'mystery swine disease'. 2017-02-23. Express. 2017-02-24. en.
  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. . etal . 1991 . Generation of transgenic dairy cattle using 'in vitro' embryo production . Biotechnology . 9 . 9. 844–7 . 10.1038/nbt0991-844 . 1367358 . 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. Web site: Cloned bull could contribute to development of disease-resistant African cattle . ILRI news . 2016-09-05 . 2021-07-24.
  26. Book: Pal . Aruna . A. K. . Chakravarty . Genetics and breeding for disease resistance of livestock . . London, United Kingdom . 22 October 2019 . 978-0-12-817267-4 . 1125327298 . 271–296 . 208596567 . 10.1016/b978-0-12-816406-8.00019-x. p.276
  27. Web site: Fluorescent puppy is world's first transgenic dog . 23 April 2009. New Scientist .
  28. Web site: World's First Transgenic Dog-Fluorescent 'Ruppy' . 2009-04-24 .
  29. News: Super-strong, genetically-engineered dogs -- Could they cure Parkinson's disease?. 28 October 2015. Will Heilpern. CNN.
  30. News: First Gene-Edited Dogs Reported in China. Technology Review. 19 October 2015. Antonio Regalado.
  31. News: Glowing monkeys 'to aid research' . 27 May 2009. BBC News. 2009-05-28 . Jason . Palmer.
  32. Cyranoski . D . Newly created transgenic primate may become an alternative disease model to rhesus macaques . 2009 . 10.1038/459492a . Nature. 19478751 . 459 . 7246 . 492. free .
  33. Okano. Hideyuki. Partha. Mitra. Brain-mapping projects using the common marmoset. Neuroscience Research. April 2015. 93. 3–7. 10.1016/j.neures.2014.08.014. 25264372. free.
  34. Eric Poeschla . Wongsrikeao P, Saenz D, Rinkoski T, Otoi T, Poeschla E . Antiviral restriction factor transgenesis in the domestic cat . Nature Methods . 2011 . 10.1038/nmeth.1703 . 8 . 10 . 853–9 . 21909101 . 4006694.
  35. Staff (3 April 2012) Biology of HIV National Institute of Allergy and Infectious Diseases, Retrieved 31 August 2012

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