A novelkitmutant rat enables hematopoietic stem cell engraftment without irradiation

Summary Hematopoietic stem cell (HSC) transplantation is extensively studied in mouse models, but their limited scale presents challenges for effective engraftment and comprehensive evaluations. Rats, due to their larger size and anatomical similarity to humans, offer a promising alternative. In this study, we establish a rat model with the Kit V834M mutation, mirroring Kit W41 mice often used in KIT signaling and HSC research. Kit V834M rats are viable and fertile, displaying anemia and mast cell depletion similar to Kit W41 mice. The mutation affects myeloid cell proliferation and differentiation, as seen in the colony-forming unit granulocyte-macrophage assay. Importantly, Kit V834M rats support donor rat-HSC engraftment without irradiation. Competitive transplantation assays reveal reduced reconstruction capacity in Kit V834M HSCs. Leveraging the larger scale of this rat model enhances our understanding of HSC biology and transplantation dynamics, potentially advancing our knowledge in this field.