Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout
Abstract Infectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87658-5 |
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| author | Mari Raudstein Ma. Michelle D. Peñaranda Erik Kjærner-Semb Søren Grove H. Craig Morton Rolf Brudvik Edvardsen |
| author_facet | Mari Raudstein Ma. Michelle D. Peñaranda Erik Kjærner-Semb Søren Grove H. Craig Morton Rolf Brudvik Edvardsen |
| author_sort | Mari Raudstein |
| collection | DOAJ |
| description | Abstract Infectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleosts, including Atlantic salmon. In this study, we used CRISPR/Cas9 technology to knock out the two IgM genes in Atlantic salmon. High-throughput sequencing revealed an average mutagenesis efficiency of 97% across both loci, with a predominance of frameshift mutations (78%). Gene expression analyses demonstrated significantly reduced membrane-bound IgM mRNA levels in head kidney and spleen tissues. Flow cytometry revealed a 78% reduction in IgM+ B cells in peripheral blood, and Western blot analyses showed decreased IgM protein levels in serum. Notably, an upregulation of IgT mRNA was observed, suggesting a potential compensatory mechanism. This work presents the first application of CRISPR/Cas9 to disrupt an immune-related gene in the F0 generation of Atlantic salmon, and lays the foundation for generating a model completely lacking IgM+ B cells which can be used to study the role of B cells and antibodies. This study has implications for advancing immune research in teleosts and for developing strategies to improve salmon health and welfare in aquaculture. |
| format | Article |
| id | doaj-art-82d1d4b5fdf14f639a0f345bd04596e3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-82d1d4b5fdf14f639a0f345bd04596e32025-02-02T12:17:11ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87658-5Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockoutMari Raudstein0Ma. Michelle D. Peñaranda1Erik Kjærner-Semb2Søren Grove3H. Craig Morton4Rolf Brudvik Edvardsen5Institute of Marine ResearchInstitute of Marine ResearchInstitute of Marine ResearchInstitute of Marine ResearchInstitute of Marine ResearchInstitute of Marine ResearchAbstract Infectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleosts, including Atlantic salmon. In this study, we used CRISPR/Cas9 technology to knock out the two IgM genes in Atlantic salmon. High-throughput sequencing revealed an average mutagenesis efficiency of 97% across both loci, with a predominance of frameshift mutations (78%). Gene expression analyses demonstrated significantly reduced membrane-bound IgM mRNA levels in head kidney and spleen tissues. Flow cytometry revealed a 78% reduction in IgM+ B cells in peripheral blood, and Western blot analyses showed decreased IgM protein levels in serum. Notably, an upregulation of IgT mRNA was observed, suggesting a potential compensatory mechanism. This work presents the first application of CRISPR/Cas9 to disrupt an immune-related gene in the F0 generation of Atlantic salmon, and lays the foundation for generating a model completely lacking IgM+ B cells which can be used to study the role of B cells and antibodies. This study has implications for advancing immune research in teleosts and for developing strategies to improve salmon health and welfare in aquaculture.https://doi.org/10.1038/s41598-025-87658-5Adaptive immunityGene editingAquacultureVaccinesImmunoglobulinIgT |
| spellingShingle | Mari Raudstein Ma. Michelle D. Peñaranda Erik Kjærner-Semb Søren Grove H. Craig Morton Rolf Brudvik Edvardsen Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout Scientific Reports Adaptive immunity Gene editing Aquaculture Vaccines Immunoglobulin IgT |
| title | Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout |
| title_full | Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout |
| title_fullStr | Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout |
| title_full_unstemmed | Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout |
| title_short | Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout |
| title_sort | generation of igm b cell deficient atlantic salmon salmo salar by crispr cas9 mediated igm knockout |
| topic | Adaptive immunity Gene editing Aquaculture Vaccines Immunoglobulin IgT |
| url | https://doi.org/10.1038/s41598-025-87658-5 |
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