A novel Kit mutant rat enables hematopoietic stem cell engraftment without irradiation

Hematopoietic stem cell (HSC) transplantation is extensively studied in mouse models, but their limited scale presents challenges for effective engraftment and comprehensive evaluations. Rats, owing to their larger size and anatomical similarity to humans, offer a promising alternative. In this study, we establish a rat model with the KitV834M mutation, mirroring KitW41 mice often used in KIT signaling and HSC research. KitV834M rats are viable and fertile, displaying anemia and mast cell depletion similar to KitW41 mice. The colony-forming unit assay revealed that the KitV834M mutation leads to reduced proliferation and loss of or decreased pluripotency of hematopoietic stem and progenitor cells (HSPCs), resulting in diminished competitive repopulating capacity of KitV834M HSPCs in competitive transplantation assays. Importantly, KitV834M rats support donor rat-HSC engraftment without irradiation. Leveraging the larger scale of this rat model enhances our understanding of HSC biology and transplantation dynamics, potentially advancing our knowledge in this field.