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Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse.
Dev Biol. 2002 Apr 15; 244(2):305-18.DB

Abstract

In recent years, the Cre integrase from bacteriophage P1 has become an essential tool for conditional gene activation and/or inactivation in mouse. In an earlier report, we described a fusion protein between Cre and a mutated form of the ligand binding domain of the estrogen receptor (Cre-ER) that renders Cre activity tamoxifen (TM) inducible, allowing for conditional modification of gene activity in the mammalian neural tube in utero. In the current work, we have generated a transgenic mouse line in which Cre-ER is ubiquitously expressed to permit temporally regulated Cre-mediated recombination in diverse tissues of the mouse at embryonic and adult stages. We demonstrate that a single, intraperitoneal injection of TM into a pregnant mouse at 8.5 days postcoitum leads to detectable recombination in the developing embryo within 6 h of injection and efficient recombination of a reporter gene in derivatives of all three germ layers within 24 h of injection. In addition, by varying the dose of TM injected, the percentage of cells undergoing a recombination event in the embryo can be controlled. Dose-dependent excision induced by TM was also possible in diverse tissues in the adult mouse, including the central nervous system, and in cultured cells derived from the transgenic mouse line. This inducible Cre system will be a broadly useful tool to modulate gene activity in mouse embryos, adults, and culture systems where temporal control is an important consideration.

Authors+Show Affiliations

Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11944939

Citation

Hayashi, Shigemi, and Andrew P. McMahon. "Efficient Recombination in Diverse Tissues By a Tamoxifen-inducible Form of Cre: a Tool for Temporally Regulated Gene Activation/inactivation in the Mouse." Developmental Biology, vol. 244, no. 2, 2002, pp. 305-18.
Hayashi S, McMahon AP. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol. 2002;244(2):305-18.
Hayashi, S., & McMahon, A. P. (2002). Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Developmental Biology, 244(2), 305-18.
Hayashi S, McMahon AP. Efficient Recombination in Diverse Tissues By a Tamoxifen-inducible Form of Cre: a Tool for Temporally Regulated Gene Activation/inactivation in the Mouse. Dev Biol. 2002 Apr 15;244(2):305-18. PubMed PMID: 11944939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. AU - Hayashi,Shigemi, AU - McMahon,Andrew P, PY - 2002/4/12/pubmed PY - 2002/6/1/medline PY - 2002/4/12/entrez SP - 305 EP - 18 JF - Developmental biology JO - Dev Biol VL - 244 IS - 2 N2 - In recent years, the Cre integrase from bacteriophage P1 has become an essential tool for conditional gene activation and/or inactivation in mouse. In an earlier report, we described a fusion protein between Cre and a mutated form of the ligand binding domain of the estrogen receptor (Cre-ER) that renders Cre activity tamoxifen (TM) inducible, allowing for conditional modification of gene activity in the mammalian neural tube in utero. In the current work, we have generated a transgenic mouse line in which Cre-ER is ubiquitously expressed to permit temporally regulated Cre-mediated recombination in diverse tissues of the mouse at embryonic and adult stages. We demonstrate that a single, intraperitoneal injection of TM into a pregnant mouse at 8.5 days postcoitum leads to detectable recombination in the developing embryo within 6 h of injection and efficient recombination of a reporter gene in derivatives of all three germ layers within 24 h of injection. In addition, by varying the dose of TM injected, the percentage of cells undergoing a recombination event in the embryo can be controlled. Dose-dependent excision induced by TM was also possible in diverse tissues in the adult mouse, including the central nervous system, and in cultured cells derived from the transgenic mouse line. This inducible Cre system will be a broadly useful tool to modulate gene activity in mouse embryos, adults, and culture systems where temporal control is an important consideration. SN - 0012-1606 UR - https://www.unboundmedicine.com/medline/citation/11944939/Efficient_recombination_in_diverse_tissues_by_a_tamoxifen_inducible_form_of_Cre:_a_tool_for_temporally_regulated_gene_activation/inactivation_in_the_mouse_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S001216060290597X DB - PRIME DP - Unbound Medicine ER -