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Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice.

Publication ,  Journal Article
Lee, C-L; Moding, EJ; Huang, X; Li, Y; Woodlief, LZ; Rodrigues, RC; Ma, Y; Kirsch, DG
Published in: Dis Model Mech
May 2012

The site-specific recombinases Cre and Flp can mutate genes in a spatially and temporally restricted manner in mice. Conditional recombination of the tumor suppressor gene p53 using the Cre-loxP system has led to the development of multiple genetically engineered mouse models of human cancer. However, the use of Cre recombinase to initiate tumors in mouse models limits the utilization of Cre to genetically modify other genes in tumor stromal cells in these models. To overcome this limitation, we inserted FRT (flippase recognition target) sites flanking exons 2-6 of the endogenous p53 gene in mice to generate a p53(FRT) allele that can be deleted by Flp recombinase. We show that FlpO-mediated deletion of p53 in mouse embryonic fibroblasts impairs the p53-dependent response to genotoxic stress in vitro. In addition, using FSF-Kras(G12D/+); p53(FRT/FRT) mice, we demonstrate that an adenovirus expressing FlpO recombinase can initiate primary lung cancers and sarcomas in mice. p53(FRT) mice will enable dual recombinase technology to study cancer biology because Cre is available to modify genes specifically in stromal cells to investigate their role in tumor development, progression and response to therapy.

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Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

May 2012

Volume

5

Issue

3

Start / End Page

397 / 402

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Neoplasms
  • Mice, Transgenic
  • Mice
  • Humans
  • Gene Targeting
  • Fibroblasts
  • Embryo, Mammalian
  • Developmental Biology
  • DNA Nucleotidyltransferases
 

Citation

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Lee, C.-L., Moding, E. J., Huang, X., Li, Y., Woodlief, L. Z., Rodrigues, R. C., … Kirsch, D. G. (2012). Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice. Dis Model Mech, 5(3), 397–402. https://doi.org/10.1242/dmm.009084
Lee, Chang-Lung, Everett J. Moding, Xiaofang Huang, Yifan Li, Loretta Z. Woodlief, Rafaela C. Rodrigues, Yan Ma, and David G. Kirsch. “Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice.Dis Model Mech 5, no. 3 (May 2012): 397–402. https://doi.org/10.1242/dmm.009084.
Lee C-L, Moding EJ, Huang X, Li Y, Woodlief LZ, Rodrigues RC, et al. Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice. Dis Model Mech. 2012 May;5(3):397–402.
Lee, Chang-Lung, et al. “Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice.Dis Model Mech, vol. 5, no. 3, May 2012, pp. 397–402. Pubmed, doi:10.1242/dmm.009084.
Lee C-L, Moding EJ, Huang X, Li Y, Woodlief LZ, Rodrigues RC, Ma Y, Kirsch DG. Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice. Dis Model Mech. 2012 May;5(3):397–402.
Journal cover image

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

May 2012

Volume

5

Issue

3

Start / End Page

397 / 402

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Neoplasms
  • Mice, Transgenic
  • Mice
  • Humans
  • Gene Targeting
  • Fibroblasts
  • Embryo, Mammalian
  • Developmental Biology
  • DNA Nucleotidyltransferases