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PLoS One. 2009;4(1):e4286. doi: 10.1371/journal.pone.0004286. Epub 2009 Jan 27.

Split-cre complementation indicates coincident activity of different genes in vivo.

Author information

1
Faculty of Medicine, Interdisciplinary Centre for Clinical Research, IZKF,University of Leipzig, Leipzig, Germany. johannes.hirrlinger@medizin.uni-leipzig.de

Abstract

Cre/LoxP recombination is the gold standard for conditional gene regulation in mice in vivo. However, promoters driving the expression of Cre recombinase are often active in a wide range of cell types and therefore unsuited to target more specific subsets of cells. To overcome this limitation, we designed inactive "split-Cre" fragments that regain Cre activity when overlapping co-expression is controlled by two different promoters. Using transgenic mice and virus-mediated expression of split-Cre, we show that efficient reporter gene activation is achieved in vivo. In the brain of transgenic mice, we genetically defined a subgroup of glial progenitor cells in which the Plp1- and the Gfap-promoter are simultaneously active, giving rise to both astrocytes and NG2-positive glia. Similarly, a subset of interneurons was labelled after viral transfection using Gad67- and Cck1 promoters to express split-Cre. Thus, split-Cre mediated genomic recombination constitutes a powerful spatial and temporal coincidence detector for in vivo targeting.

PMID:
19172189
PMCID:
PMC2628726
DOI:
10.1371/journal.pone.0004286
[Indexed for MEDLINE]
Free PMC Article

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