| Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis. | |
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MedLine Citation:
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PMID: 20959604 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Natalie J Foot; Yew Ann Leong; Loretta E Dorstyn; Hazel E Dalton; Kristen Ho; Lin Zhao; Michael D Garrick; Baoli Yang; Devendra Hiwase; Sharad Kumar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-19 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 638-46 Citation Subset: AIM; IM |
Affiliation:
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Department of Hematology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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