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.
journal_name
Naturejournal_title
Natureauthors
Skarnes WC,Rosen B,West AP,Koutsourakis M,Bushell W,Iyer V,Mujica AO,Thomas M,Harrow J,Cox T,Jackson D,Severin J,Biggs P,Fu J,Nefedov M,de Jong PJ,Stewart AF,Bradley Adoi
10.1038/nature10163subject
Has Abstractpub_date
2011-06-15 00:00:00pages
337-42issue
7351eissn
0028-0836issn
1476-4687pii
nature10163journal_volume
474pub_type
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