HEME-REGULATED EUKARYOTIC INITIATION FACTOR 2 ALPHA KINASE KNOCKOUT MICE AND METHODS FOR USE

摘要

The targeted disruption of the gene encoding the heme-regulated eIF2-kinase(HRI) in mice establishes that HRI, which is expressed predominantly inerythroid cells, regulates the synthesis of both alpha and beta globins in redblood cell precursors by inhibiting the general translation initiation factoreIF2. HRI is a physiological regulator of gene expression in the erythroidlineage and acts both as a sensor of heme and an effector controlling theinitiation of translation. Accordingly regulation of HRI can be used tocontrol proliferation of cells, especially cells of hematopoietic origin,using compositions and compounds identified using HRI deficient mice.