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Molecular and Cellular Biology, May 2005, p. 3896-3905, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.3896-3905.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficiency of RNA Interference in the Mouse Hematopoietic System Varies between Cell Types and Developmental Stages

Philipp Oberdoerffer,1* Chryssa Kanellopoulou,2 Vigo Heissmeyer,1 Corinna Paeper,3 Christine Borowski,4 Iannis Aifantis,5 Anjana Rao,1 and Klaus Rajewsky1*

The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115,1 The Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115,2 The Australian National University, Canberra, Australian Capital Territory 0200, Australia,3 Department of Pathology, University of Chicago, Chicago, Illinois 60637,4 Department of Medicine, University of Chicago, Chicago, Illinois 606375

Received 8 February 2005/ Accepted 10 February 2005

RNA interference (RNAi) is a naturally occurring posttranscriptional gene-silencing mechanism that has been adapted as a genetic tool for loss-of-function studies of a variety of organisms. It is more widely applicable than classical gene targeting and allows for the simultaneous inactivation of several homologous genes with a single transgene. Recently, RNAi has been used for conditional and conventional gene inactivation in mice. Unlike gene targeting, RNAi is a dynamic process, and its efficiency may vary both between cell types and throughout development. Here we demonstrate that RNAi can be used to target three separately encoded isoforms of the bcl-2 family gene bfl-1/A1 in a conditional manner in mice. The extent of gene inactivation varies between different cell types and is least efficient in mature lymphocytes. Our data suggest that RNAi is affected by factors beyond small interfering RNA-mRNA stoichiometry.

* Corresponding author. Present address for Philipp Oberdoerffer: Department of Pathology, Harvard Medical School, NRB, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: (617) 432-3932. Fax: (617) 432-6225. E-mail: philober{at}hms.harvard.edu. Mailing address for Klaus Rajewsky: The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115. Phone: (617) 278-3067. Fax: (617) 278-3129. E-mail: rajewsky{at}cbr.med.harvard.edu.

Molecular and Cellular Biology, May 2005, p. 3896-3905, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.3896-3905.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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