A novelkitmutant rat enables hematopoietic stem cell engraftment without irradiation

Abstract

SummaryHematopoietic 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 theKitV834Mmutation, mirroringKitW41mice often used in KIT signaling and HSC research.KitV834Mrats are viable and fertile, displaying anemia and mast cell depletion similar toKitW41mice. The mutation affects myeloid cell proliferation and differentiation, as seen in the colony-forming unit granulocyte-macrophage assay. Importantly,KitV834Mrats support donor rat-HSC engraftment without irradiation. Competitive transplantation assays reveal reduced reconstruction capacity inKitV834MHSCs. Leveraging the larger scale of this rat model enhances our understanding of HSC biology and transplantation dynamics, potentially advancing our knowledge in this field.