Proto-oncogene c-KIT, also known as tyrosine-protein kinase KIT, CD117 or mast/stem cell growth factor receptor (SCFR), is a receptor tyrosine kinase protein that in humans is encoded by the KIT gene. KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. The NCG-X mouse is a next-generation immunodeficient model developed by introducing a W41 point mutation from Val to Met at position 831 into the c-Kit (CD117) gene on the NCG background. This mutation impairs c-Kit receptor function, a key signaling protein involved in the survival, proliferation, and differentiation of hematopoietic stem cells (HSCs). As a result, mice carrying this mutation exhibit spontaneous anemia and suppressed murine endogenous HSC function, providing a unique advantage for human HSC transplantation.

The underlying NCG strain carries Prkdc and IL2rg gene knockouts, resulting in severe immunodeficiency with complete absence of T cells, B cells, and NK cells. By combining this with the c-Kit^W41 mutation, NCG-X mice allow for efficient engraftment of human CD34⁺ HSCs without the need for irradiation preconditioning, a common requirement in traditional humanized mouse models to deplete host hematopoietic cells.