NRF1 and anemia (phenotype): Another non-cell-autonomous defect in global Nrf1−/− embryos (created by knocking-in to yield Nrf1rPGK-neo such that its DNA- binding domain-encoding sequence was disrupted in most of the distinct Nrf1 isoforms) leads to the lethality at mid-late gestation (i.e., E13.5–E16.5) from severe anemia, which results from abnormal maturation of precursor cells in fetal liver microenvironment [26].