We here present a novel highly efficient MDS xenotransplantation model, in humanized immunodeficient “MISTRG” mice, expressing humanized M-CSF, IL3/GM-CSF, SIRP alpha, and Thrombopoietin in the Rag−/−, IL2Rγ−/− genetic background from their endogenous murine loci. The gene discussed is IL2RG; the disease is myelodysplastic syndrome.