While a lack of EPO-EPOR signaling causes embryonic lethality with severe anemia (Wu et al., 1995; Lin et al., 1996), the brain-specific knockout of EPOR from the late embryonic phase (using EPOR-floxed mice crossed with human GFAP-Cre mice) and selective EPOR knock-in in the hematopoietic tissues of EPOR-null mice cause only a small defect in brain development (Suzuki et al., 2002; Tsai et al., 2006; Chen et al., 2007), suggesting that EPO signaling is not deeply associated with brain development. This evidence concerns the gene EPO and anemia (phenotype).