Format

Send to

Choose Destination
See comment in PubMed Commons below
Blood Cells Mol Dis. 2006 Mar-Apr;36(2):283-7. Epub 2006 Feb 15.

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

Author information

1
Section on Human Iron Metabolism, Cell Biology and Metabolism Branch National Institute of Child Health and Human Development Bethesda, MD 20892, USA. srsmith@cnmc.org

Abstract

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-onset neurodegeneration. Mice with homozygous deletion of IRP1 develop no overt abnormalities, but mice that lack both copies of IRP2 and one copy of IRP1 develop a more severe anemia and neurodegeneration than mice with deletion of IRP2 alone. Here, we have demonstrated that IRP1-/- IRP2-/- embryos do not survive gestation, and that although IRP1-/- IRP2-/blastocysts can be genotyped and harvested, implanted embryos with the IRP1-/- IRP2-/genotype are undetectable at embryonic day 6.5 and beyond. Blastocysts derived from a cross in which 25% of the fertilized embryos were expected to have the IRP1-/- IRP2-/genotype often showed brown discoloration and abnormal morphology. These abnormal blastocysts likely have the IRP1-/- IRP2-/- genotype, and the brown discoloration may be attributable to ferritin overexpression and sequestration of ferric iron in ferritin, whereas abnormal morphology may be due to concomitant functional iron deficiency. These results demonstrate that IRPs are indispensable for regulation of mammalian iron homeostasis at the post-implantation stage of murine embryonic development.

PMID:
16480904
DOI:
10.1016/j.bcmd.2005.12.006
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center