Generation of foxn1/Casper Mutant Zebrafish for Allograft and Xenograft of Normal and Malignant Cells

Summary Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employing the line for hematopoietic stem cell (HSC) transplantation (HSCT), we could achieve nonconditioned transplantation. Meanwhile, we found that fetal HSCs from 3 days post fertilization zebrafish embryos produce a better transplant outcome in foxn1/Casper mutants, compared with adult HSCs. In addition to HSCT, the foxn1/Casper mutant is feasible for allografts of myelodysplastic syndrome-like and muscle cells, as well as xenografts of medaka muscle cells. In summary, foxn1/Casper mutants permit the nonconditioned engraftment of multiple cell types and visualized characterization of transplanted cells in vivo.
Graphical Abstract
Highlights • foxn1/Casper mutant zebrafish permit unconditioned and visualized cell transplantation • Zebrafish fetal HSCs possess more robust engraftment ability than adult HSCs • foxn1/Casper mutant zebrafish permit allogeneic MDS-like cell transplantation • Allograft and xenograft of muscle cells can be monitored in foxn1/Casper mutant zebrafish
In this article, Liu and colleagues generated a foxn1/Casper mutant zebrafish line with immunodeficiency and transparency to permit allograft and xenograft of normal and malignant cells without preconditioning. In addition, they evaluated the engraftment efficiency of HSCs from different developmental stages in foxn1/Casper recipients. Additional applications included the engraftment of MDS-like cells and xenogenic medaka muscle cells.