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Proc Natl Acad Sci U S A. Aug 1, 1992; 89(15): 6861–6865.
PMCID: PMC49604

Tissue- and site-specific DNA recombination in transgenic mice.

Abstract

We have developed a method of specifically modifying the mammalian genome in vivo. This procedure comprises heritable tissue-specific and site-specific DNA recombination as a function of recombinase expression in transgenic mice. Transgenes encoding the bacteriophage P1 Cre recombinase and the loxP-flanked beta-galactosidase gene were used to generate transgenic mice. Genomic DNA from doubly transgenic mice exhibited tissue-specific DNA recombination as a result of Cre expression. Further characterization revealed that this process was highly efficient at distinct chromosomal integration sites. These studies also imply that Cre-mediated recombination provides a heritable marker for mitoses following the loss of Cre expression. This transgene-recombination system permits unique approaches to in vivo studies of gene function within experimentally defined spatial and temporal boundaries.

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Selected References

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  • Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol. 1981 Aug 25;150(4):467–486. [PubMed]
  • Argos P, Landy A, Abremski K, Egan JB, Haggard-Ljungquist E, Hoess RH, Kahn ML, Kalionis B, Narayana SV, Pierson LS, 3rd, et al. The integrase family of site-specific recombinases: regional similarities and global diversity. EMBO J. 1986 Feb;5(2):433–440. [PMC free article] [PubMed]
  • Craig NL. The mechanism of conservative site-specific recombination. Annu Rev Genet. 1988;22:77–105. [PubMed]
  • Abremski K, Hoess R, Sternberg N. Studies on the properties of P1 site-specific recombination: evidence for topologically unlinked products following recombination. Cell. 1983 Apr;32(4):1301–1311. [PubMed]
  • Abremski K, Hoess R. Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem. 1984 Feb 10;259(3):1509–1514. [PubMed]
  • Sauer B. Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1987 Jun;7(6):2087–2096. [PMC free article] [PubMed]
  • Sauer B, Henderson N. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5166–5170. [PMC free article] [PubMed]
  • Sauer B, Henderson N. Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucleic Acids Res. 1989 Jan 11;17(1):147–161. [PMC free article] [PubMed]
  • Golic KG, Lindquist S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell. 1989 Nov 3;59(3):499–509. [PubMed]
  • Sauer B, Henderson N. Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase. New Biol. 1990 May;2(5):441–449. [PubMed]
  • O'Gorman S, Fox DT, Wahl GM. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science. 1991 Mar 15;251(4999):1351–1355. [PubMed]
  • Dale EC, Ow DW. Gene transfer with subsequent removal of the selection gene from the host genome. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10558–10562. [PMC free article] [PubMed]
  • Chaffin KE, Beals CR, Wilkie TM, Forbush KA, Simon MI, Perlmutter RM. Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. EMBO J. 1990 Dec;9(12):3821–3829. [PMC free article] [PubMed]
  • MacGregor GR, Caskey CT. Construction of plasmids that express E. coli beta-galactosidase in mammalian cells. Nucleic Acids Res. 1989 Mar 25;17(6):2365–2365. [PMC free article] [PubMed]
  • Marth JD, Peet R, Krebs EG, Perlmutter RM. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Garvin AM, Abraham KM, Forbush KA, Farr AG, Davison BL, Perlmutter RM. Disruption of thymocyte development and lymphomagenesis induced by SV40 T-antigen. Int Immunol. 1990;2(2):173–180. [PubMed]
  • Abraham KM, Levin SD, Marth JD, Forbush KA, Perlmutter RM. Thymic tumorigenesis induced by overexpression of p56lck. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3977–3981. [PMC free article] [PubMed]
  • Cooke MP, Abraham KM, Forbush KA, Perlmutter RM. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell. 1991 Apr 19;65(2):281–291. [PubMed]
  • Brinster RL, Palmiter RD. Introduction of genes into the germ line of animals. Harvey Lect. 1984 1985;80:1–38. [PubMed]
  • Jaenisch R. Transgenic animals. Science. 1988 Jun 10;240(4858):1468–1474. [PubMed]
  • Hanahan D. Transgenic mice as probes into complex systems. Science. 1989 Dec 8;246(4935):1265–1275. [PubMed]
  • Golic KG. Site-specific recombination between homologous chromosomes in Drosophila. Science. 1991 May 17;252(5008):958–961. [PubMed]
  • Capecchi MR. Altering the genome by homologous recombination. Science. 1989 Jun 16;244(4910):1288–1292. [PubMed]

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