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.
Hirrlinger
Johannes
J
Faculty of Medicine, Interdisciplinary Centre for Clinical Research, IZKF,University of Leipzig, Leipzig, Germany. johannes.hirrlinger@medizin.uni-leipzig.de
Scheller
Anja
A
Hirrlinger
Petra G
PG
Kellert
Beate
B
Tang
Wannan
W
Wehr
Michael C
MC
Goebbels
Sandra
S
Reichenbach
Andreas
A
Sprengel
Rolf
R
Rossner
Moritz J
MJ
Kirchhoff
Frank
F
D000818:Animals; D019742:Chemokines, CC; D000229:Dependovirus / Q000235:genetics; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D005968:Glutamate Decarboxylase / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D019426:Integrases / Q000235:genetics*; D007395:Interneurons / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009457:Neuroglia / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011949:Receptors, Cholecystokinin / Q000235:genetics; D013234:Stem Cells / Q000166:cytology
C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D011949:Receptors, Cholecystokinin; C045073:Cre recombinase; D019426:Integrases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1