A mouse model for visualization and conditional mutations in the erythroid lineage.

Hematologic disorders can be caused by sporadic or inherited mutations. However, the molecular mechanisms that lead to pathogenicity are only partially understood. An accurate method to generate mouse models is conditional gene manipulation facilitated by the Cre-loxP recombination system. To enable identification and genomic manipulation of erythroid progenitor cells, we established a knock-in mouse model (ErGFPcre) that expresses an improved GFPcre fusion protein controlled by the endogenous erythropoietin receptor (EpoR) promoter. We show that ErGFPcre mice enable the identification of GFP-positive erythroid progenitor cells and the highly specific genomic manipulation of the erythroid lineage. Analysis of GFP-positive erythroid progenitor cells suggests a developmental switch in lineage progression from the hematopoietic stem cell compartment to early erythroid progenitor cells that are stem cell antigen-1-negative (Sca-1(-)) and c-kit(high). Within the hematopoietic system, Cre-mediated recombination is limited to erythroid progenitor cells and occurs in the adult bone marrow at a frequency of up to 80% and in the fetal liver with an efficiency close to 100%. Differential transcriptional activity of the wild-type and the knock-in locus was observed in nonhematopoietic tissues. Thus, our ErGFPcre mouse model could promote the identification of regulatory elements controlling nonhematopoietic EpoR expression and facilitates the characterization and genomic manipulation of erythroid progenitor cells.