title: 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.
authors: Department of Genetics, The Scripps Research Institute, La Jolla, CA, USA.
authors: Lara
authors: L
authors: Krieg
authors: Oren
authors: O
authors: Milstein
authors: Philippe
authors: P
authors: Krebs
authors: Yu
authors: Y
authors: Xia
authors: Bruce
authors: B
authors: Beutler
authors: Xin
authors: X
authors: Du
mesh_terms: D000126:Achlorhydria / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D019943:Amino Acid Substitution; D018798:Anemia, Iron-Deficiency / Q000178:diet therapy / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D004195:Disease Models, Animal; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption; D019266:Iron, Dietary / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009153:Mutagens / Q000494:pharmacology; D009996:Osmotic Fragility; D017354:Point Mutation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000201:enzymology* / Q000473:pathology
chemical_list: D019266:Iron, Dietary; D009153:Mutagens; D021122:Protein Subunits; D017506:H(+)-K(+)-Exchanging ATPase; D005038:Ethylnitrosourea