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A conditional knockout resource for the genome-wide study of mouse gene function

Author

Listed:
  • William C. Skarnes

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Barry Rosen

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Anthony P. West

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Manousos Koutsourakis

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Wendy Bushell

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Vivek Iyer

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Alejandro O. Mujica

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton
    Present addresses: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA (A.O.M.); RIKEN Omics Science Center, Yokohama City, Japan (J.S.); Hopkirk Institute, Massey University, New Zealand (P.B.).)

  • Mark Thomas

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Jennifer Harrow

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Tony Cox

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • David Jackson

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

  • Jessica Severin

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton
    Present addresses: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA (A.O.M.); RIKEN Omics Science Center, Yokohama City, Japan (J.S.); Hopkirk Institute, Massey University, New Zealand (P.B.).)

  • Patrick Biggs

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton
    Present addresses: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA (A.O.M.); RIKEN Omics Science Center, Yokohama City, Japan (J.S.); Hopkirk Institute, Massey University, New Zealand (P.B.).)

  • Jun Fu

    (Biotechnologisches Zentrum, TU Dresden)

  • Michael Nefedov

    (Children’s Hospital Oakland Research Institute)

  • Pieter J. de Jong

    (Children’s Hospital Oakland Research Institute)

  • A. Francis Stewart

    (Biotechnologisches Zentrum, TU Dresden)

  • Allan Bradley

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton)

Abstract

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.

Suggested Citation

  • William C. Skarnes & Barry Rosen & Anthony P. West & Manousos Koutsourakis & Wendy Bushell & Vivek Iyer & Alejandro O. Mujica & Mark Thomas & Jennifer Harrow & Tony Cox & David Jackson & Jessica Sever, 2011. "A conditional knockout resource for the genome-wide study of mouse gene function," Nature, Nature, vol. 474(7351), pages 337-342, June.
    • Handle: RePEc:nat:nature:v:474:y:2011:i:7351:d:10.1038_nature10163
    DOI: 10.1038/nature10163
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    7. Delfina M. Romero & Karine Poirier & Richard Belvindrah & Imane Moutkine & Anne Houllier & Anne-Gaëlle LeMoing & Florence Petit & Anne Boland & Stephan C. Collins & Mariano Soiza-Reilly & Binnaz Yalci, 2022. "Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
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    12. Chrysafis Vogiatzis & Mustafa Can Camur, 2019. "Identification of Essential Proteins Using Induced Stars in Protein–Protein Interaction Networks," INFORMS Journal on Computing, INFORMS, vol. 31(4), pages 703-718, October.

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