Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are two cytosolic
proteins that maintain cellular
iron homeostasis by binding to
RNA stem loops known as
iron responsive elements (IREs) that are found in the
untranslated regions of target mRNAs that encode
proteins involved in
iron metabolism. IRPs modify the expression of
iron metabolism genes, and global and tissue-specific knockout mice have been made to evaluate the physiological significance of these
iron regulatory proteins (Irps). Here, we will discuss the results of the studies that have been performed with mice engineered to lack the expression of one or both Irps and made in different strains using different methodologies. Both Irp1 and Irp2 knockout mice are viable, but the double knockout (Irp1(-/-)Irp2(-/-)) mice die before birth, indicating that these Irps play a crucial role in maintaining
iron homeostasis. Irp1(-/-) mice develop
polycythemia and
pulmonary hypertension, and when these mice are challenged with a low
iron diet, they die early of abdominal
hemorrhages, suggesting that Irp1 plays an essential role in erythropoiesis and in the pulmonary and cardiovascular systems. Irp2(-/-) mice develop microcytic
anemia,
erythropoietic protoporphyria and a progressive
neurological disorder, indicating that Irp2 has important functions in the nervous system and erythropoietic homeostasis. Several excellent review articles have recently been published on Irp knockout mice that mainly focus on Irp1(-/-) mice (referenced in the introduction). In this review, we will briefly describe the phenotypes and physiological implications of Irp1(-/-) mice and discuss the phenotypes observed for Irp2(-/-) mice in detail with a particular emphasis on the neurological problems of these mice.