Since knock-out of Epo and EpoR genes result in severe anemia and premature death at E13.5, the role of Epo-EpoR signaling in non-hematopoietic tissue was difficult to study until Suzuki et al. [115] generated a transgene-rescue EpoR knock-out mouse that rescued EpoR expression exclusively in the hematopoietic lineage (hematopoietic-rescued EpoR knock-out). Here, EPO is linked to anemia.