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Precise CRISPR/Cas9 Editing of the NHE1 Gene Renders Chickens Resistant to the J Subgroup of Avian Leukosis Virus

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    0521805 - ÚMG 2021 RIV US eng J - Journal Article
    Koslová, Anna - Trefil, P. - Mucksová, J. - Reinišová, Markéta - Plachý, Jiří - Kalina, J. - Kučerová, Dana - Geryk, Josef - Krchlíková, Veronika - Lejčková, B. - Hejnar, Jiří
    Precise CRISPR/Cas9 Editing of the NHE1 Gene Renders Chickens Resistant to the J Subgroup of Avian Leukosis Virus.
    Proceedings of the National Academy of Sciences of the United States of America. Roč. 117, č. 4 (2020), s. 2108-2012. ISSN 0027-8424. E-ISSN 1091-6490
    R&D Projects: GA ČR GA15-23993S; GA MŠMT LO1419; GA MZe(CZ) QK1810344
    Institutional support: RVO:68378050
    Keywords : CRISPR/Cas9 genome editing in chicken * Na+/H+ exchanger type 1 * avian leukosis virus subgroup J * disease resilience in poultry * primordial germ cells
    OECD category: Virology
    Impact factor: 11.205, year: 2020
    Method of publishing: Open access
    https://www.pnas.org/content/117/4/2108

    Avian leukosis virus subgroup J (ALV-J) is an important concern for the poultry industry. Replication of ALV-J depends on a functional cellular receptor, the chicken Na+/H+ exchanger type 1 (chNHE1). Tryptophan residue number 38 of chNHE1 (W38) in the extracellular portion of this molecule is a critical amino acid for virus entry. We describe a CRISPR/Cas9-mediated deletion of W38 in chicken primordial germ cells and the successful production of the gene-edited birds. The resistance to ALV-J was examined both in vitro and in vivo, and the ΔW38 homozygous chickens tested ALV-J-resistant, in contrast to ΔW38 heterozygotes and wild-type birds, which were ALV-J-susceptible. Deletion of W38 did not manifest any visible side effect. Our data clearly demonstrate the antiviral resistance conferred by precise CRISPR/Cas9 gene editing in the chicken. Furthermore, our highly efficient CRISPR/Cas9 gene editing in primordial germ cells represents a substantial addition to genotechnology in the chicken, an important food source and research model.
    Permanent Link: http://hdl.handle.net/11104/0306370

     
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    PNAS_A_Koslova_2019.pdf4801.1 KBAuthor´s preprintrequire
     
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