In a groundbreaking study, scientists at the Institute of Marine Research have successfully used CRISPR/Cas9 technology to delete both immunoglobulin M (IgM) genes in Atlantic salmon (Salmo salar). This is the first time an immune gene has been specifically deleted in this species.
The research, published in Scientific Reports, has implications for advancing immunological research in teleost fish and for developing strategies to improve the health and welfare of salmon in aquaculture.
The challenge of infectious diseases in aquaculture
Infectious diseases are a major concern in the global salmon industry, leading to substantial economic losses and reduced animal welfare. Vaccination is the primary strategy for disease prevention, but its efficacy varies, particularly against viral pathogens. A deeper understanding of immune responses in salmon is essential for developing more effective vaccines.
IgM and its role in immunity
Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleost fish, including Atlantic salmon. It exists in two forms: a membrane-bound form on the surface of B cells and a secreted form found in serum. IgM plays a crucial role in fighting pathogens by binding to antigens and triggering B cell activation, which leads to the production of soluble antibodies.
Gene editing with CRISPR/Cas9
CRISPR/Cas9 is a revolutionary gene-editing technology that allows scientists to make precise alterations to genomic DNA. In this study, researchers used CRISPR/Cas9 to target and disrupt the two IgM genes in Atlantic salmon. They achieved a high mutagenesis efficiency of 97% at both loci, with a predominance of frameshift mutations (78%).
This study is the first report of a knockout of an immune-related gene in Atlantic salmon in vivo. While CRISPR/Cas9 technology has been used to study immunity genes in salmon cell lines, this study applies it to the whole organism.
Effects of IgM knockout
The knockout of IgM resulted in significantly reduced levels of membrane-bound IgM mRNA in head kidney, kidney, and spleen tissues. Flow cytometry analysis revealed a 78% reduction in IgM+ B cells in peripheral blood. Western blot analysis showed decreased levels of IgM protein in serum. Interestingly, an upregulation of IgT mRNA was observed, suggesting a possible compensatory mechanism.
Implications for salmon health and aquaculture
The generation of IgM knockout Atlantic salmon provides a valuable model for studying the role of B cells and antibodies in combating pathogens. The implications for the salmon industry of the study on IgM knockout in Atlantic salmon using CRISPR/Cas9 are significant and varied:
- Improved Vaccine Development: A better understanding of IgM’s role in the immune response paves the way for developing more effective vaccines. This study enables the differentiation between antibody-mediated and non-antibody-mediated protection, which is crucial for designing vaccines that induce the appropriate immune response against specific pathogens. The salmon industry could benefit from vaccines that offer broader and more robust protection against various diseases.
- Reduced Economic Losses: Infectious diseases are a major challenge in the salmon industry, causing economic losses and reducing animal welfare. Creating an IgM-deficient salmon model helps to better understand the immunological mechanisms activated in response to pathogens and vaccines. This knowledge is fundamental for developing more effective disease control strategies and reducing economic losses associated with infectious outbreaks.
- Advances in Immunological Research: This study, being the first report of an immune gene knockout in Atlantic salmon in vivo, lays the foundation for further research into the teleost immune system. The IgM-deficient fish model allows for studying the specific role of IgM and other immunoglobulins, such as IgT, in the immune response. This is important because salmonids have specific immunological differences compared to other teleosts.
- Development of Challenge Models: The IgM-deficient salmon model can be used to create challenge models that allow for evaluating the effectiveness of new vaccines and treatments in an immunodeficient context. These models are important for better understanding the immune response to pathogens and accelerating the development of disease control strategies.
Future studies could focus on generating a complete IgM+ B cell knockout model by breeding the F0 generation of IgM crispants. This model will enable further investigation of the role of IgM in the immune response and potential compensatory mechanisms involving IgT.
Conclusion
This study marks a significant advance in our understanding of the teleost immune system and provides a powerful tool for improving the health and welfare of salmon in aquaculture. The successful deletion of IgM in Atlantic salmon demonstrates the potential of CRISPR/Cas9 technology for targeted genetic alteration in this species.
Contact
Rolf Brudvik Edvardsen
Institute of Marine Research
Bergen, Norway
Email: rolfbe@hi.no
Reference (open access)
Raudstein, M., Peñaranda, M. M., Grove, S., Morton, H. C., & Edvardsen, R. B. (2025). Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout. Scientific Reports, 15(1), 1-13. https://doi.org/10.1038/s41598-025-87658-5
