Journal article
Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis
Blood, Vol.117(2), pp.638-646
01/13/2011
DOI: 10.1182/blood-2010-07-295287
PMID: 20959604
Abstract
The divalent metal ion transporter DMT1 is critical for nonheme iron import. We have previously shown that DMT1 is regulated in vitro by ubiquitination that is facilitated by the adaptor proteins Ndfip1 and Ndfip2. Here we report that in Ndfip1(-/-) mice fed a low-iron diet, DMT1 expression and activity in duodenal enterocytes are significant higher than in the wild-type animals. This correlates with an increase in serum iron levels and transferrin saturation. Liver and spleen iron stores were also increased in Ndfip1(-/-) mice fed a normal diet. Counter-intuitive to the increase in iron uptake, Ndfip1(-/-) mice fed a low iron diet develop severe microcytic, hypochromic anemia. We demonstrate that this is due to a combination of iron deficiency and inflammatory disease in Ndfip1(-/-) mice, because Ndfip1(-/-)/Rag1(-/-) immunodeficient mice fed a low iron diet did not develop anemia and showed an iron overload phenotype. These data demonstrate that Ndfip1 is a critical mediator of DMT1 regulation in vivo, particularly under iron restricted conditions. (Blood. 2011;117(2):638-646)
Details
- Title: Subtitle
- Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis
- Creators
- Natalie J. Foot - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaYew Ann Leong - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaLoretta E. Dorstyn - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaHazel E. Dalton - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaKristen Ho - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaLin Zhao - SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USAMichael D. Garrick - SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USABaoli Yang - University of Iowa, BioVentures CenterDevendra Hiwase - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, AustraliaSharad Kumar - SA Pathol, Dept Hematol, Ctr Canc Biol, Adelaide, SA, Australia
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.117(2), pp.638-646
- Publisher
- Amer Soc Hematology
- DOI
- 10.1182/blood-2010-07-295287
- PMID
- 20959604
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Number of pages
- 9
- Grant note
- 508085 / National Health and Medical Research Council of Australia; National Health and Medical Research Council (NHMRC) of Australia
- Language
- English
- Date published
- 01/13/2011
- Academic Unit
- BioVentures Center; Obstetrics and Gynecology
- Record Identifier
- 9983557534802771
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