title: Gastrin-deficient mice have disturbed hematopoiesis in response to iron deficiency.
abstract: Gastrins are peptide hormones important for gastric acid secretion and growth of the gastrointestinal mucosa. We have previously demonstrated that ferric ions bind to gastrins, that the gastrin-ferric ion complex interacts with the iron transport protein transferrin in vitro, and that circulating gastrin concentrations positively correlate with transferrin saturation in vivo. Here we report the effect of long-term dietary iron modification on gastrin-deficient (Gas(-/-)) and hypergastrinemic cholecystokinin receptor 2-deficient (Cck2r(-/-)) mice, both of which have reduced basal gastric acid secretion. Iron homeostasis in both strains appeared normal unless the animals were challenged by iron deficiency. When fed an iron-deficient diet, Gas(-/-) mice, but not Cck2r(-/-) mice, developed severe anemia. In iron-deficient Gas(-/-) mice, massive splenomegaly was also apparent with an increased number of splenic megakaryocytes accompanied by thrombocytosis. The expression of the mRNA encoding the iron-regulatory peptide hepcidin, Hamp, was down-regulated in both Cck2r(-/-) and Gas(-/-) mice on a low-iron diet, but, interestingly, the reduction was greater in Cck2r(-/-) mice and smaller in Gas(-/-) mice than in the corresponding wild-type strains. These data suggest that gastrins play an important direct role, unrelated to their ability to stimulate acid secretion, in hematopoiesis under conditions of iron deficiency.
authors.affiliation: University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria 3084, Australia. kovacs@unimelb.edu.au
authors.forename: Suzana
authors.initials: S
authors.lastname: Kovac
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Arthur
authors.initials: A
authors.lastname: Shulkes
authors.forename: Graham S
authors.initials: GS
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D004921:Erythropoietin / Q000097:blood; D005755:Gastrins / Q000097:blood / Q000172:deficiency*; D006410:Hematopoiesis; D064451:Hepcidins; D000090463:Iron Deficiencies; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D043887:Receptor, Cholecystokinin B / Q000502:physiology; D013163:Splenomegaly / Q000209:etiology; D013926:Thrombopoietin / Q000097:blood; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D004921:Erythropoietin; D005755:Gastrins; D064451:Hepcidins; D043887:Receptor, Cholecystokinin B; D013926:Thrombopoietin; D000099236:Solute Carrier Family 11, Member 2; C579599:Hamp protein, mouse