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Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice.

ABSTRACT: Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea-induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase α subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis.

SUBMITTER: Krieg L

PROVIDER: S-EPMC3236123 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice.

Krieg Lara L Milstein Oren O Krebs Philippe P Xia Yu Y Beutler Bruce B Du Xin X

Blood 20111005 24

Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea-induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused ...[more]

PMID: 21976678

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