Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2.

Microcytic anemia, erythropoietic protoporphyria and neurodegeneration in mice with targeted deletion of iron regulatory protein 2 Running title: iron-limited erythropoiesis in mice with IRP2 deletion

RED CELLS Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2

Iron-regulatory proteins (IRPs) 1 and 2 posttranscriptionally regulate expression of transferrin receptor (TfR), ferritin, and other iron metabolism proteins. Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues. Despite this misregulation, there are no apparent pathologic consequences in tissues such as the liver and kidney. However...

RED CELLS hem6: an ENU-induced recessive hypochromic microcytic anemia mutation in the mouse

Mouse models have proven invaluable for understanding erythropoiesis. Here, we describe an autosomal recessive, inherited anemia in the mouse mutant hem6. Hematologic and transplantation analyses reveal a mild, congenital, hypochromic, microcytic anemia intrinsic to the hematopoietic system that is associated with a decreased red blood cell zinc protoporphyrin to heme ratio, indicative of porph...

Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice.

Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway, experience a painful type of skin photosensitivity called erythropoietic protoporphyria (EPP), which is caused by the excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial results have been reported regarding hematologic status and iron status of patients with EPP. We t...

Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development.

Iron regulatory proteins 1 and 2 (IRPs) are homologous mammalian cytosolic proteins that sense intracellular iron levels and post-transcriptionally regulate expression of ferritin, transferrin receptor, and other iron metabolism proteins. Adult mice with homozygous targeted deletion of IRP2 develop microcytic anemia, elevated red cell protoporphyrin IX levels, high serum ferritin, and adult-ons...