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The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis.

Publication ,  Journal Article
Zhang, M; Kirsch, DG
Published in: Dis Model Mech
September 2015

Novel genetically engineered mouse models using the Cre-loxP or the Flp-FRT systems have generated useful reagents to manipulate the mouse genome in a temporally-regulated and tissue-specific manner. By incorporating a constitutive Cre driver line into a mouse model in which FRT-regulated genes in other cell types are regulated by Flp-FRT recombinase, gene expression can be manipulated simultaneously in separate tissue compartments. This application of dual recombinase technology can be used to dissect the role of stromal cells in tumor development and cancer therapy. Generating mice in which Cre-ER(T2) is expressed under Flp-FRT-mediated regulation would enable step-wise manipulation of the mouse genome using dual recombinase technology. Such next-generation mouse models would enable sequential mutagenesis to better model cancer and define genes required for tumor maintenance. Here, we generated novel genetically engineered mice that activate or delete Cre-ER(T2) in response to Flp recombinase. To potentially utilize the large number of Cre-loxP-regulated transgenic alleles that have already been targeted into the Rosa26 locus, such as different reporters and mutant genes, we targeted the two novel Cre-ER(T2) alleles into the endogenous Col1a1 locus for ubiquitous expression. In the Col1a1(FRT-Cre-ER-T2-FRT) mice, Flp deletes Cre-ER(T2), so that Cre-ER(T2) is only expressed in cells that have never expressed Flp. In contrast, in the Col1a1(FRT-STOP-FRT-Cre-ER-T2) mice, Flp removes the STOP cassette to allow Cre-ER(T2) expression so that Cre-ER(T2) is only expressed in cells that previously expressed Flp. These two new novel mouse strains will be complementary to each other and will enable the exploration of complex biological questions in development, normal tissue homeostasis and cancer.

Duke Scholars

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Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

September 2015

Volume

8

Issue

9

Start / End Page

1155 / 1166

Location

England

Related Subject Headings

  • Tamoxifen
  • Mutation
  • Mutagenesis
  • Microscopy, Fluorescence
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Integrases
  • Homeostasis
 

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Zhang, M., & Kirsch, D. G. (2015). The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis. Dis Model Mech, 8(9), 1155–1166. https://doi.org/10.1242/dmm.021204
Zhang, Minsi, and David G. Kirsch. “The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis.Dis Model Mech 8, no. 9 (September 2015): 1155–66. https://doi.org/10.1242/dmm.021204.
Zhang, Minsi, and David G. Kirsch. “The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis.Dis Model Mech, vol. 8, no. 9, Sept. 2015, pp. 1155–66. Pubmed, doi:10.1242/dmm.021204.
Journal cover image

Published In

Dis Model Mech

DOI

EISSN

1754-8411

Publication Date

September 2015

Volume

8

Issue

9

Start / End Page

1155 / 1166

Location

England

Related Subject Headings

  • Tamoxifen
  • Mutation
  • Mutagenesis
  • Microscopy, Fluorescence
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Integrases
  • Homeostasis