Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing (original) (raw)

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Acknowledgements

The authors thank C. Morton and A. Hawkins from the Brigham and Women's Cytogenetics Core and R. Bronson from the DF/HCC Rodent Pathology Core for technical assistance and discussions. The authors thank F. Zhang for providing the CRISPR-Cas components. The authors also thank A. Schambach, E. Charpentier, J. Kroenke and A. Mullally for useful discussions, and thank S. Schwartz and B. Haas for assistance with analysis of sequencing data. C. Baum and A. Schambach of the Hannover Medical School, Hannover, Germany, kindly provided RRL.PPT.SFFV.IRES.eGFP.pre*, and D. Trono of EPFL, Lausanne, Switzerland, kindly provided both pMD2.G (Addgene plasmid 12259) and psPAX2 (Addgene plasmid 12260). This work was supported by funding from the National Institutes of Health (P01 CA108631), a Leukemia and Lymphoma Society Scholar Award, the SPARC consortium, a Center for Excellence in Genome Science grant (5P50HG006193-02 from the National Human Genome Research Institute) (A.R.) and Klarman Family Foundation at The Broad Institute (A.R.). D.H. was funded by the German Cancer Foundation (Mildred-Scheel Fellowship). M.S.K. is an EMBO and European Hematology Association Fellow.

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Author notes

  1. Dirk Heckl
    Present address: Current address: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.,
  2. Monika S Kowalczyk and David Yudovich: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Dirk Heckl, David Yudovich, Roger Belizaire, Rishi V Puram, Marie E McConkey & Benjamin L Ebert
  2. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
    Monika S Kowalczyk, Anne Thielke, Aviv Regev & Benjamin L Ebert
  3. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Roger Belizaire & Jon C Aster
  4. Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Aviv Regev

Authors

  1. Dirk Heckl
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  2. Monika S Kowalczyk
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  3. David Yudovich
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  4. Roger Belizaire
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  5. Rishi V Puram
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  6. Marie E McConkey
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  7. Anne Thielke
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  8. Jon C Aster
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  9. Aviv Regev
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  10. Benjamin L Ebert
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Contributions

D.H., M.S.K. and B.L.E. designed experiments. D.H., M.S.K., D.Y., R.B., R.V.P., M.E.C. and A.T. performed the experiments. D.H., M.S.K., D.Y., R.B., J.C.A., A.R. and B.L.E. analyzed and interpreted the data. D.H. and B.L.E. wrote the manuscript.

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Correspondence toBenjamin L Ebert.

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Heckl, D., Kowalczyk, M., Yudovich, D. et al. Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing.Nat Biotechnol 32, 941–946 (2014). https://doi.org/10.1038/nbt.2951

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