DOI QR코드

DOI QR Code

Current Progress in Generation of Genetically Modified Mice

유전자 조작 마우스 개발의 최신 연구 동향

  • Song, Ki-Duk (NICHD/National Institutes of Health) ;
  • Cho, Byung-Wook (College of Natural Resources & Life Science/PNU-IGB Joint Research Center, National University)
  • 송기덕 (미국립보건원) ;
  • 조병욱 (부산대학교 생명자원과학대학 생명자원과학부)
  • Published : 2007.04.25

Abstract

Manipulation of the mouse genome by activating or inactivating the gene has contributed to the understanding of the function of the gene in the subset of cells during embryonic development or postnatal period of life. Most of all, gene targeting, which largely depends on the availability of mouse embryonic stem (ES) cells, is the milestone of development of animal models for human disease. Recombinase-mediated genome modification (Cre-LoxP and Flp-Frt etc) and the ligand-dependent regulation system, more accurate and elaborate manipulation tools, have been successfully developed and applied to dissect the mechanisms governing complex biological processes and to understand the role of protein in temporal-and spatial aspects of development. As technologies concerning refined manipulation of mouse genome are developed, they are expected to open new opportunities to better understand the diverse in vivo functions of genes.

생쥐 유전자를 과발현 시키거나 제거하는 유전자 조작 기술의 발달은 배 발생 단계나 출생 후 특정한 세포에서의 특정 단계에서의 유전자 기능을 이해하는 많은 기여를 하고 있다. 특히, 높은 상동 재조합 활성을 가지는 생쥐 배 줄기세포를 이용한 유전자 적중 기법은 인간 질환을 이해하는데 필수적인 동물 모델 개발에 중요한 기여를 하였다. 최근에는 Cre과 Flp와 같은 염기서열 특이적 재조합 효소와 라이겐드에 의한 조절 시스템의 도입으로 좀 더 정확하고 정교한 유전자 발현 조절을 위해 개발되어 복잡한 생명현상을 지배하는 메카니즘과 시간과 공간에서 작동하는 유전자의 기능을 이해하는데 많은 기여를 하고 있다. 마우스 게놈을 세밀하게 조작할 수 있는 새로운 분자생물학적 도구의 적용으로 in vivo상에서 유전자의 다양한 기능을 좀 더 정확하게 이해할 수 있는 기회가 열릴 것으로 기대된다.

Keywords

References

  1. Ahn, S. and A. L. Joyner. 2004. Dynamic Changes in the Response of Cells to Positive Hedgehog Signaling during Mouse Limb Patterning. Cell 118 (4), 505-516 https://doi.org/10.1016/j.cell.2004.07.023
  2. Bedell, M. A., N. A. Jenkins and N. G. Copeland. 1997. Mouse models of human disease. Part I: techniques and resources for genetic analysis in mice.1: Genes Dev.11(1), 1-10 https://doi.org/10.1101/gad.11.1.1
  3. Behringer, R. and T. Magnuson. 2000. Tissue specific expression of Cre recombinase in mice (Special Issue). In: Genesis. Wiley-Liss. vol. 26, issue
  4. Brocard, J., X. Warot, O. Wendling, N. Messaddeq, J. L. Vonesch, P. Chambon and D. Metzger. 1997. Spatio-temporally controlled site-specific somatic mutagenesis in the mouse. Proc. Natl. Acad. Sci. USA 94, 14559-14563 https://doi.org/10.1073/pnas.94.26.14559
  5. Buchholz, F., P. O. Angrand and A. F. Stewart. 1998. Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol 16, 657-662 https://doi.org/10.1038/nbt0798-657
  6. Cheah, S. S. and R. R. Behringer. 2001. Contemporary gene targeting strategies for the novice. Mol. Biotechnol. 19, 297-304 https://doi.org/10.1385/MB:19:3:297
  7. Chen, C. M. and R. R. Behringer. 2001. CREating breakthroughs. Nat Biotechnol. 19, 921-922 https://doi.org/10.1038/nbt1001-921
  8. Dong, J. and G. W. Stuart. 2004. Transgene manipulation in zebrafish by using recombinase. Methods Cell Biol. 77, 363-379 https://doi.org/10.1016/S0091-679X(04)77020-X
  9. Erman, B., A. S. Alag, O. Dahle, F. van Laethem, S. D. Sarafova, T. L. Guinter, S. O. Sharrow, A. Grinberg, P. E. Love and A. Singer. 2006. Coreceptor signal strength regulates positive selection but does not determine CD4/ CD8 lineage choice in a physiologic in vivo model. J. Immunol. 177(10), 6613-6625 https://doi.org/10.4049/jimmunol.177.10.6613
  10. Farley, F. W., P. Soriano, L. S. Steffen, and S. M. Dymecki. 2000. Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28, 106-110 https://doi.org/10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.0.CO;2-T
  11. Feil, R., J. Brocard, B. Mascrez, M. LeMeur, D. Metzger and P. Chambon. 1996. Ligand-activated site-specific recombination in mice. Proc. Natl. Acad. Sci. USA 93, 10887-10890 https://doi.org/10.1073/pnas.93.20.10887
  12. Fontenot, J. D, J. P. Rasmussen, L. M. Williams, J. L. Dooley, A. G. Farr and A. Y. Rudensky. 2005. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3), 329-341 https://doi.org/10.1016/j.immuni.2005.01.016
  13. Gu, H., D. Marth, P. C. Orban, H. Mossmann, and K. Rajewsky. 1994. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265, 103-106 https://doi.org/10.1126/science.8016642
  14. Hasty, P., A. Abuin and A. Bradley. 2000. Gene targeting, principles, and practice in mammalian cells. In: Gene Targeting: A Practical Approach (2nd ed.), edited by Joyner AL. New York: Oxford University Press, chapt. 1, p. 1-35
  15. Hogan, B., R. Beddington, F. Costantini, and E. Lacy. 1994. Manipulating the mouse embryo. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
  16. Indra, A. K., X. Warot, J. Brocard, J. M. Bornert, J. H. Xiao, P. Chambon and D. Metzger. 1999. Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic. Acids. Res. 27, 4324-4327 https://doi.org/10.1093/nar/27.22.4324
  17. Jo, D., A. Nashabi, C. Doxsee, Q. Lin, D. Unutmaz, J. Chen and H. E. Ruley. 2001. Epigenetic regulation of gene structure and function with a cell-permeable Cre recombinase. Nat. Biotechnol. 19, 929-933 https://doi.org/10.1038/nbt1001-929
  18. Joshi, S. K., K. Hashimoto, and P. A. Koni. 2002. Induced DNA recombination by Cre recombinase protein transduction. Genesis 33, 48-54 https://doi.org/10.1002/gene.10089
  19. Kim, D. G., H. M. Kang, S. K. Jang and H. S. Shin. 1992. Construction of a bifunctional mRNA in the mouse by using the internal ribosomal entry site of the encephalomyocarditis virus. Mol. Cell. Biol. 12, 3636-3643 https://doi.org/10.1128/MCB.12.8.3636
  20. Kobayashi, T., Y. Kida, T. Kaneko, I. Pastan and K. Kobayashi. 2001. Efficient ablation by immunotoxin-mediated cell targeting of the cell types that express human interleukin-2 receptor depending on the internal ribosome entry site. J. Gene. Med. 3, 505-510 https://doi.org/10.1002/jgm.208
  21. Li M, A. K. Indra, X. Warot, J. Brocard, N. Messaddeq, S. Kato, D. Metzger and P. Chambon. 2000. Skin abnormalities generated by temporally controlled RXR mutations in mouse epidermis. Nature 407, 633-636 https://doi.org/10.1038/35036595
  22. Mansouri, A., P. Pla, L. Larue, and P. Gruss. 2001. Pax3 acts cell autonomously in the neural tube and somites by controlling cell surface properties. Development 128, 1995-2005
  23. McGuire, S. E., G. Roman and R. L. Davis. 2004. Gene expression systems in Drosophila: a synthesis of time and space. Trends Genet. 20, 384-391 https://doi.org/10.1016/j.tig.2004.06.012
  24. Metzger, D. and P. Chambon. 2001. Site- and time-specific gene targeting in the mouse. 1: Methods 24(1), 71-80 https://doi.org/10.1006/meth.2001.1159
  25. Orban, P. C., D. Chui and J. D. Marth. 1992. Tissue- and site-specific DNA recombination in transgenic mice. Proc. Natl. Acad. Sci. USA. 89, 8971-8976 https://doi.org/10.1073/pnas.89.19.8971
  26. Peitz, M., K. Pfannkuche, K. Rajewsky and F. Edenhofer. 2002. Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: a tool for efficient genetic engineering of mammalian genomes. Proc. Natl. Acad. Sci. USA 99, 4489-4494 https://doi.org/10.1073/pnas.032068699
  27. Pelletier, J. and N. Sonenberg. 1989. Internal binding of eucaryotic ribosomes on poliovirus RNA: translation in HeLa cell extracts. J. Virol. 63, 441-444
  28. Rodriguez, C. I., F. Buchholz, J. Galloway, R. Sequerra, J. Kasper, R. Ayala, A. F. Stewart and S. M. Dymecki. 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-LoxP. Nat. Genet. 25, 139-140 https://doi.org/10.1038/75973
  29. Srivastava, V. and D. W. Ow. 2004. Maker-free site-specific gene integration in plants. Trends Biotechnol. 22, 627-629 https://doi.org/10.1016/j.tibtech.2004.10.002
  30. Stemberg, N. and D. Hamilton. 1981. Bacteriophage P1 site-specific recombination.1. Recombination between LoxP sites. J. Mol. Biol. 150, 467-486 https://doi.org/10.1016/0022-2836(81)90375-2
  31. van der Weyden, L., D. J. Adams and A. Bradley. 2002. Tools for targeted manipulation of the mouse genome. Physiol. Genomics 11, 133-164 https://doi.org/10.1152/physiolgenomics.00074.2002
  32. Volkert, F. C., L. C Wu, P. A. Fisher and J. R. Broach. Survival strategies of the yeast plasmid two-micron circle. Basic Life Sci. 40, 375-396
  33. Werdien, D., G. Pelier and G. U. Ryffel. 2001. FLP and Cre recombinase function on Xenopus embryos. Nucleic Acids Res. 29, e53 https://doi.org/10.1093/nar/29.11.e53