The NCG-X mouse model, engineered with a c-Kit gene mutation to enhance hematopoietic stem cell (HSC) engraftment, supports research on genetic medicine for erythroid-related diseases. Compared to the HSC-NCG model, NCG-X mice exhibit robust human erythrocyte and platelet development in both bone marrow and peripheral blood post-human HSC engraftment. Targeted elimination of host-derived macrophages further enhances human erythrocyte and platelet production in these mice. This model offers a unique platform for evaluating gene therapies targeting erythroid disorders, combining immune-deficient features with improved erythroid and platelet reconstitution. It holds promise for advancing gene therapy research and pharmacological interventions in erythroid-related diseases.