Split-Cre Complementation Indicates Coincident Activity of Different Genes In Vivo
By J. Hirrlinger, A. Scheller, P. Hirrlinger, B. Kellert, Wannan Tang, M. C. Wehr, S. Goebbels, André Reichenbach, R. Sprengel, M. Rossner and 1 more. 2009
153 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Neurology
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Citations in the corpus
- Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance (2015, unknown): “However, there are still other approaches with unique merits that we have not tested, such as split-Cre (Casanova et al., 2003; Hirrlinger et al., 2009; Wang et al., 2012) or the creation of Flp, Dre or tTA-dependent Cre driver lines, which could be applied to the many existing floxed alleles.”
- In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. (2010, methodology): “Because two different promoters control the expression of the two Cre fragments, only cells coexpressing the two markers have functional Cre-recombinase, and will therefore undergo the genomic recombination and permanently express the reporter gene (Hirrlinger et al., 2009).”