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

Abstract

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 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 colony-forming unit assay revealed that the Kit^V834M 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 Kit^V834M HSPCs in competitive transplantation assays. Importantly, Kit^V834M 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.