Temporal, spatial, and cell type-specific control of Cre-mediated DNA recombination in transgenic mice.
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 beta-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.
Utomo
A R
AR
Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Dr., San Antonio, TX 78245-3207, USA.
Nikitin
A Y
AY
Lee
W H
WH
D000818:Animals; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D019426:Integrases / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators; D019076:Transgenes; D014764:Viral Proteins
D015534:Trans-Activators; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D013752:Tetracycline; D004318:Doxycycline