Transgenic Animals

Transgenesis implies that a foreign DNA fragment is introduced into the genome of a multicellular organism and transmitted to progeny. Transgenesis therefore differs from gene transfer into cultured cells (transfection) or into the somatic cells of a patient (gene therapy).

Keywords: gene addition; gene replacement; cloning; microinjection; animal models; animal bioreactors; animals as organ donors; improved farm animals

Figure 1. The generation of transgenic animals by gene microinjection. The embryos obtained by superovulation or by in vitro fertilization receive the foreign genes and are developed in foster mothers. Transgenes are detected and transmitted to progeny by normal reproduction. PCR, polymerase chain reaction.
Figure 2. The mechanisms leading to the random integration of a foreign gene into an animal genome. The foreign DNA sequences recognize short and partially homologous regions of the genome. Reparation mechanisms integrate the foreign DNA. Before integration, a homologous recombination mechanism generates polymers of the foreign gene organized in tandem.
Figure 3. The experimental protocol leading to specific gene replacement. A gene construct containing two long regions strictly homologous to the targeted host gene and containing a foreign DNA region transferred to cells. The homologous sequences recombine and the targeted gene is replaced by the foreign gene. The cells in which gene replacement occurred are saved by double selection (not shown here).
Figure 4. The transmission of a mutation by the generation of chimaeric animals. The mutipotent embryonic cells in which gene replacement occurred are transferred into a recipient embryo and participate in its development. The mutation can be transmitted to progeny.
Figure 5. The transmission of a mutation by the cloning technique. The fetal cells in which gene addition or replacement occurred are used to generate living embryos after transfer into enucleated oocytes. The mutation is transmitted to progeny.
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 Further Reading
    book Clarke AR (2002) Transgenesis Techniques: Principles and Protocols, 2nd edn. Totowa, NJ: Humana Press.
    Giraldo P, Rival-Gervier S, Houdebine LM and Montoliu L (2003) The potential benefits of insulators on heterologous constructs in transgenic animals. Transgenic Research 12: 751–755.
    book Houdebine LM (1999) "Ethical implications of knock-out and transgenesis techniques for animal research". In: Crusio WE and Gerlai RT (eds) Handbook of Molecular Genetic Technique for Brain and Behaviour Research (Techniques in Behaviour Research), vol. 13, pp. 936–948. Amsterdam: Elsevier.
    Houdebine LM (2000) Transgenic animal bioreactors. Transgenic Research 9: 305–320.
    Houdebine LM (2002) Transgenesis to improve animal production. Livestock Production Science 74: 255–268.
    book Houdebine LM (2003) Animal Transgenesis and Cloning. Chichester: John Wiley and Sons.
    book Houdebine LM, Attal J and Vilotte JL (2002) "Vector design for transgene expression". In: Pinkert CA (ed.) Transgenic Animal Technology, 2nd edn, pp. 419–458. London: Academic Press.
    McManus MT and Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics 3: 737–747.
    Phelps CJ, Koike C, Vaught TD et al. (2003) Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 299: 411–414.
    book Pinkert CA (2002) Transgenic Animal Technology, 2nd edn. London: Academic Press.
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Houdebine, Louis Marie(May 2005) Transgenic Animals. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003839]