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Temporal, spatial, and cell type–specific control of Cre-mediated DNA recombination in transgenic mice

Nature Biotechnology volume 17, pages 1091–1096 (1999)Cite this article

Abstract

We have developed a universal system for temporal, spatial, and cell type–specific control of gene expression in mice that (1) integrates the advantages of tetracycline-controlled gene expression and Cre-recombinase-loxP site-mediated gene inactivation, and (2) simplifies schemes of animal crosses by combination of two control elements in a single transgene. Two transgenic strains were generated in which the cell type–specific control was provided by either the retinoblastoma gene promoter or the whey acidic protein promoter. Both promoters drive the expression of the reverse tetracycline-controlled transactivator (rtTA). Placed in cis configuration to the rtTA transcription unit, the rtTA-inducible promoter directs expression of Cre recombinase. In both strains crossed with cActXstopXLacZ reporter mice, which have a loxP-stop of transcription/translation-loxP-LacZ cassette driven by chicken β-actin promoter, Cre-loxP-mediated DNA recombination leading to LacZ expression was accurately regulated in a temporal, spatial, and cell type-specific manner. This approach can be applied to establishment of analogous mouse strains with virtually any promoter as systems to control gene regulation in a variety of cell types.

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Figure 1: Experimental design.
Figure 2: Conditional expression of LacZ mediated by doxycycline-induced Cre recombinase.
Figure 3: Expression of LacZ and Rb striated muscles of the thigh after administration of doxycycline.
Figure 4: Doxycycline-induced Cre-mediated DNA recombination in TgWAPrtTACre, cActXstopXLacZ mice.

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Acknowledgements

We thank Drs. Hua Gu, Manfred Gossen, and Jeffrey M. Rosen for generous gifts of plasmids pIC-Cre, pUHD, and pBL-103, respectively, and Dr. Chia-Yang Liu for assistance during early stages of the project. We are also grateful to Dr. David J. Anderson for the cActXstopXLacZ reporter mice, and to Dr. Eva Y.-H.P. Lee for insightful discussions. Transgenic mice were generated in the Transgenic Core facility of the San Antonio Cancer Institute. This work was supported by NIH grants CA58318 and EY05758, and McDermott Endowment Funds.

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  1. Department of Molecular Medicine, Institute of Biotechnology The University of Texas Health Science Center at San Antonio, 15355 Lambda Dr., San Antonio, 78245-3207 , TX

    Ahmad R.H. Utomo, Alexander Yu. Nikitin & Wen-Hwa Lee

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Correspondence to Wen-Hwa Lee.

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Utomo, A., Nikitin, A. & Lee, WH. Temporal, spatial, and cell type–specific control of Cre-mediated DNA recombination in transgenic mice. Nat Biotechnol 17, 1091–1096 (1999). https://doi.org/10.1038/15073

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