Induced mitotic recombination of p53in vivo
- Wei Wang*,
- Madhuri Warren*,†, and
- Allan Bradley*,‡
- *Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; and
- †Department of Pathology, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom
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Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved January 18, 2007 (received for review September 12, 2006)
Abstract
Genetic mosaics produced by FLP/FRT induced mitotic recombination have been widely used in Drosophila to study gene function in development. Recently, the Cre/loxP system has been applied to induce mitotic recombination in mouse embryonic stem cells and in many adult mouse tissues. We have used this strategy to generate a previously undescribed p53 mouse model in which expression of a ubiquitously expressed recombinase in a heterozygous p53 knockout animal produces mitotic recombinant clones homozygous for the p53 mutation. The induction of loss of heterozygosity in a few cells in an otherwise normal tissue mimics genetic aspects of tumorigenesis more closely than existing models and has revealed the possible cell autonomous nature of Wnt3. Our results suggest that inducible mitotic recombination can be used for clonal analysis of mutants in the mouse.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: abradley{at}sanger.ac.uk
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Author contributions: W.W. and M.W. contributed equally to this work; W.W. and A.B. designed research; W.W. and M.W. performed research; W.W. contributed new reagents/analytic tools; W.W., M.W., and A.B. analyzed data; and W.W., M.W., and A.B. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS direct submission.
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See Commentary on page 4245.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0607953104/DC1.
- Abbreviation:
- LOH,
- loss of heterozygosity.
- © 2007 by The National Academy of Sciences of the USA
