Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/71652
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Type: Journal article
Title: Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis
Author: Foot, N.
Leong, Y.
Dorstyn, L.
Dalton, H.
Ho, K.
Zhao, L.
Garrick, M.
Yang, B.
Hiwase, D.
Kumar, S.
Citation: Blood, 2011; 117(2):638-646
Publisher: Amer Soc Hematology
Issue Date: 2011
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Natalie J. Foot, Yew Ann Leong, Loretta E. Dorstyn, Hazel E. Dalton, Kristen Ho, Lin Zhao, Michael D. Garrick, Baoli Yang, Devendra Hiwase, and Sharad Kumar
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. Counterintuitive 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.
Keywords: Animals
Mice, Knockout
Mice
Anemia, Iron-Deficiency
Inflammation
Iron
Iron, Dietary
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Cation Transport Proteins
Membrane Proteins
Microscopy, Confocal
Immunoblotting
Immunohistochemistry
Reverse Transcriptase Polymerase Chain Reaction
Homeostasis
Mass Spectrometry
Rights: © 2011 by The American Society of Hematology
DOI: 10.1182/blood-2010-07-295287
Appears in Collections:Aurora harvest
Medicine publications

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