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

Lara Krieg, Oren Milstein, Philippe Krebs, Yu Xia, Bruce Beutler, Xin Du

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6418-6425
Number of pages8
JournalBlood
Volume118
Issue number24
DOIs
StatePublished - Dec 8 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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