A genetically modified rodent, comprising: a nucleic acid sequence that encodes a human erythropoietin protein (hEPO), wherein the nucleic acid is operably linked to an endogenous erythropoietin gene promoter at the rodent EPO gene locus, wherein the operable linkage results in a null mutation in the rodent EPO gene at the rodent EPO gene locus, and wherein the rodent expresses additional human proteins selected from the group consisting of: a hM-CSF protein encoded by a nucleic acid under the control of an M-csf promoter wherein the M-csf promoter is an endogenous rodent M-csf promoter at the rodent M-csf gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent M-csf gene, a hIL3 protein encoded by a nucleic acid under the control of an Il-3 promoter wherein the Il-3 promoter is an endogenous rodent Il-3 promoter at the rodent Il-3 gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Il-3 gene, a hGM-CSF protein encoded by a nucleic acid under the control of a Gm-csf promoter wherein the Gm-csf promoter is an endogenous rodent Gm-csf promoter at the rodent Gm-csf gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Gm-csf gene, a hTPO protein encoded by a nucleic acid under the control of a TPO promoter wherein the TPO promoter is an endogenous rodent TPO promoter at the rodent TPO gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent TPO gene, and a hSirpa protein encoded by a nucleic acid under the control of a Sirpa promoter wherein the Sirpa promoter is an endogenous rodent Sirpa promoter at the rodent Sirpa gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Sirpa gene, wherein the human proteins include at least hTPO, hIL3, hGM-CSF, and hSirpa, and wherein the rodent is immunodeficient and the immunodeficiency is caused by a deficiency for both of Rag2 and Il2rg. a hM-CSF protein encoded by a nucleic acid under the control of an M-csf promoter wherein the M-csf promoter is an endogenous rodent M-csf promoter at the rodent M-csf gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent M-csf gene, a hIL3 protein encoded by a nucleic acid under the control of an Il-3 promoter wherein the Il-3 promoter is an endogenous rodent Il-3 promoter at the rodent Il-3 gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Il-3 gene, a hGM-CSF protein encoded by a nucleic acid under the control of a Gm-csf promoter wherein the Gm-csf promoter is an endogenous rodent Gm-csf promoter at the rodent Gm-csf gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Gm-csf gene, a hTPO protein encoded by a nucleic acid under the control of a TPO promoter wherein the TPO promoter is an endogenous rodent TPO promoter at the rodent TPO gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent TPO gene, and a hSirpa protein encoded by a nucleic acid under the control of a Sirpa promoter wherein the Sirpa promoter is an endogenous rodent Sirpa promoter at the rodent Sirpa gene locus and wherein the rodent is heterozygous null or homozygous null for the rodent Sirpa gene,