title: Joining forces: first application of a rapamycin-induced dimerizable Cre system for conditional null mutant analysis in Leishmania.
abstract: Reverse genetics in Leishmania spp has gained importance beyond basic research as efforts increase to discover and validate new drug targets. Often, the most promising targets are essential for viability of the parasites, defying a genetic analysis by current gene replacement strategies. Duncan et al. demonstrate the applicability of DiCre recombination in Leishmania for induced replacement of the kinase CRK3 gene in promastigotes. DiCre gene replacement leads to the rapid loss of the gene and allows monitoring the phenotypic effects of the loss of function, eliminating the need for prolonged cultivation and selection. Implementation of the DiCre approach will allow functional genetics of the most important of Leishmania genes and is likely to boost genetic research and drug target discovery.
authors.affiliation: Institut Pasteur and INSERM U1201, Unité de Parasitologie Moléculaire et Signalisation, Paris, France.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Späth
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D058990:Molecular Targeted Therapy; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics; D059386:Reverse Genetics / Q000379:methods*; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D050737:Proto-Oncogene Proteins c-crk; C045073:Cre recombinase; D019426:Integrases; D020123:Sirolimus