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. 1995 Aug 1;92(16):7376–7380. doi: 10.1073/pnas.92.16.7376

Cre-mediated site-specific translocation between nonhomologous mouse chromosomes.

J Van Deursen 1, M Fornerod 1, B Van Rees 1, G Grosveld 1
PMCID: PMC41342  PMID: 7638200

Abstract

Chromosome rearrangements, such as large deletions, inversions, or translocations, mediate migration of large DNA segments within or between chromosomes, which can have major effects on cellular genetic control. A method for chromosome manipulation would be very useful for studying the consequences of large-scale DNA rearrangements in mammalian cells or animals. With the use of the Cre-loxP recombination system of bacteriophage P1, we induced a site-specific translocation between the Dek gene on chromosome 13 and the Can gene on chromosome 2 in mouse embryonic stem cells. The estimated frequency of Cre-mediated translocation between the nonhomologous mouse chromosomes is approximately 1 in 1200-2400 embryonic stem cells expressing Cre recombinase. These results demonstrate the feasibility of site-specific recombination systems for chromosome manipulation in mammalian cells in vivo, breaking ground for chromosome engineering.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araki K., Araki M., Miyazaki J., Vassalli P. Site-specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):160–164. doi: 10.1073/pnas.92.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chou T. B., Perrimon N. Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. Genetics. 1992 Jul;131(3):643–653. doi: 10.1093/genetics/131.3.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Copeland N. G., Jenkins N. A., Gilbert D. J., Eppig J. T., Maltais L. J., Miller J. C., Dietrich W. F., Weaver A., Lincoln S. E., Steen R. G. A genetic linkage map of the mouse: current applications and future prospects. Science. 1993 Oct 1;262(5130):57–66. doi: 10.1126/science.8211130. [DOI] [PubMed] [Google Scholar]
  4. Golic K. G. Site-specific recombination between homologous chromosomes in Drosophila. Science. 1991 May 17;252(5008):958–961. doi: 10.1126/science.2035025. [DOI] [PubMed] [Google Scholar]
  5. Gu H., Marth J. D., Orban P. C., Mossmann H., Rajewsky K. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science. 1994 Jul 1;265(5168):103–106. doi: 10.1126/science.8016642. [DOI] [PubMed] [Google Scholar]
  6. Gu H., Zou Y. R., Rajewsky K. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell. 1993 Jun 18;73(6):1155–1164. doi: 10.1016/0092-8674(93)90644-6. [DOI] [PubMed] [Google Scholar]
  7. Kilby N. J., Snaith M. R., Murray J. A. Site-specific recombinases: tools for genome engineering. Trends Genet. 1993 Dec;9(12):413–421. doi: 10.1016/0168-9525(93)90104-p. [DOI] [PubMed] [Google Scholar]
  8. Matsuzaki H., Nakajima R., Nishiyama J., Araki H., Oshima Y. Chromosome engineering in Saccharomyces cerevisiae by using a site-specific recombination system of a yeast plasmid. J Bacteriol. 1990 Feb;172(2):610–618. doi: 10.1128/jb.172.2.610-618.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Orban P. C., Chui D., Marth J. D. Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6861–6865. doi: 10.1073/pnas.89.15.6861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Qin M., Bayley C., Stockton T., Ow D. W. Cre recombinase-mediated site-specific recombination between plant chromosomes. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1706–1710. doi: 10.1073/pnas.91.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rabbitts T. H. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. doi: 10.1038/372143a0. [DOI] [PubMed] [Google Scholar]
  12. Rowley J. D., Potter D. Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood. 1976 May;47(5):705–721. [PubMed] [Google Scholar]
  13. Sauer B. Identification of cryptic lox sites in the yeast genome by selection for Cre-mediated chromosome translocations that confer multiple drug resistance. J Mol Biol. 1992 Feb 20;223(4):911–928. doi: 10.1016/0022-2836(92)90252-f. [DOI] [PubMed] [Google Scholar]
  14. Sauer B. Manipulation of transgenes by site-specific recombination: use of Cre recombinase. Methods Enzymol. 1993;225:890–900. doi: 10.1016/0076-6879(93)25056-8. [DOI] [PubMed] [Google Scholar]
  15. Yon J., Jones T., Garson K., Sheer D., Fried M. The organization and conservation of the human Surfeit gene cluster and its localization telomeric to the c-abl and can proto-oncogenes at chromosome band 9q34.1. Hum Mol Genet. 1993 Mar;2(3):237–240. doi: 10.1093/hmg/2.3.237. [DOI] [PubMed] [Google Scholar]
  16. te Riele H., Maandag E. R., Berns A. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5128–5132. doi: 10.1073/pnas.89.11.5128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. van Deursen J., Lovell-Badge R., Oerlemans F., Schepens J., Wieringa B. Modulation of gene activity by consecutive gene targeting of one creatine kinase M allele in mouse embryonic stem cells. Nucleic Acids Res. 1991 May 25;19(10):2637–2643. doi: 10.1093/nar/19.10.2637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. van Deursen J., Wieringa B. Targeting of the creatine kinase M gene in embryonic stem cells using isogenic and nonisogenic vectors. Nucleic Acids Res. 1992 Aug 11;20(15):3815–3820. doi: 10.1093/nar/20.15.3815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. von Lindern M., Fornerod M., van Baal S., Jaegle M., de Wit T., Buijs A., Grosveld G. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 1992 Apr;12(4):1687–1697. doi: 10.1128/mcb.12.4.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. von Lindern M., Fornerod M., van Baal S., Jaegle M., de Wit T., Buijs A., Grosveld G. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 1992 Apr;12(4):1687–1697. doi: 10.1128/mcb.12.4.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. von Lindern M., Poustka A., Lerach H., Grosveld G. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. Mol Cell Biol. 1990 Aug;10(8):4016–4026. doi: 10.1128/mcb.10.8.4016. [DOI] [PMC free article] [PubMed] [Google Scholar]

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