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Cell type-specific manipulation with GFP-dependent Cre recombinase.

Authors
  • Tang, Jonathan C Y
  • Rudolph, Stephanie
  • Dhande, Onkar S
  • Abraira, Victoria E
  • Choi, Seungwon
  • Lapan, Sylvain W
  • Drew, Iain R
  • Drokhlyansky, Eugene
  • Huberman, Andrew D
  • Regehr, Wade G
  • Cepko, Constance L
Type
Published Article
Journal
Nature Neuroscience
Publisher
Springer Nature
Publication Date
Sep 01, 2015
Volume
18
Issue
9
Pages
1334–1341
Identifiers
DOI: 10.1038/nn.4081
PMID: 26258682
Source
Medline
License
Unknown

Abstract

There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.

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