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

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.

Pubmed ID: 19172189


  • Hirrlinger J
  • Scheller A
  • Hirrlinger PG
  • Kellert B
  • Tang W
  • Wehr MC
  • Goebbels S
  • Reichenbach A
  • Sprengel R
  • Rossner MJ
  • Kirchhoff F


PloS one

Publication Data

January 27, 2009

Associated Grants


Mesh Terms

  • Animals
  • Chemokines, CC
  • Dependovirus
  • Genes, Reporter
  • Genetic Complementation Test
  • Glutamate Decarboxylase
  • Immunohistochemistry
  • Integrases
  • Interneurons
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Neuroglia
  • Promoter Regions, Genetic
  • Receptors, Cholecystokinin
  • Stem Cells