The importance of EPO signaling through its cognate receptor was demonstrated by the identical phenotype of EPO-null and EPOR-null mice: fetal death at embryonic day 13.5 (E13.5) associated with severe anemia and the complete lack of definitive RBCs (Wu et al., 1995; Kieran et al., 1996; Lin et al., 1996). The gene discussed is EPO; the disease is anemia (phenotype).