TARGETED DISRUPTION OF THE UBIQUITOUS CNC-BZIP TRANSCRIPTION FACTOR, NRF-1, RESULTS IN ANEMIA AND EMBRYONIC LETHALITY IN MICE

The CNC-basic leucine zipper (CNC-bZIP) family is a subfamily of bZIP proteins identified from independent searches for factors that bind th e AP-1-like cis-elements in the beta-globin locus control region, Thre e members, p45-Nf-e2, Nrf-1 and Nrf-2 have been identified in mammals. Expression of p45-Nf-e2 is largely restricted to hematopoietic cells while Nrf-1 and Nrf-2 are expressed in a wide range of tissues, To det ermine the function of Nrf-1, targeted disruption of the Nrf-1 gene wa s carried out. Homozygous Nrf-1 mutant mice are anemic due to a non-ce ll autonomous defect in definitive erythropoiesis and die in utero.