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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Bibliographic Details
Published in:Scientific Reports
Main Authors: Raudstein, Mari, Peñaranda, Ma. Michelle D., Kjærner-Semb, Erik, Grove, Søren, Morton, H. Craig, Edvardsen, Rolf Brudvik
Other Authors: Institute Of Marine Research
Format: Article in Journal/Newspaper
Language:English
Published: Springer Science and Business Media LLC 2025
Subjects:
Atlantic salmon
Salmo salar
Online Access:https://doi.org/10.1038/s41598-025-87658-5
https://www.nature.com/articles/s41598-025-87658-5.pdf
https://www.nature.com/articles/s41598-025-87658-5
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Summary: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.

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