title: Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse.
abstract: Understanding iron metabolism has been enhanced by identification of genes for iron deficiency mouse mutants. We characterized the genetics and iron metabolism of the severe anemia mutant hea (hereditary erythroblastic anemia), which is lethal at 5 to 7 days. The hea mutation results in reduced red blood cell number, hematocrit, and hemoglobin. The hea mice also have elevated Zn protoporphyrin and serum iron. Blood smears from hea mice are abnormal with elevated numbers of smudge cells. Aspects of the hea anemia can be transferred by hematopoietic stem cell transplantation. Neonatal hea mice show a similar hematologic phenotype to the flaky skin (fsn) mutant. We mapped the hea gene near the fsn locus on mouse chromosome 17 and show that the mutants are allelic. Both tissue iron overloading and elevated serum iron are also found in hea and fsn neonates. There is a shift from iron overloading to iron deficiency as fsn mice age. The fsn anemia is cured by an iron-supplemented diet, suggesting an iron utilization defect. When this diet is removed there is reversion to anemia with concomitant loss of overloaded iron stores. We speculate that the hea/fsn gene is required for iron uptake into erythropoietic cells and for kidney iron reabsorption.
authors.affiliation: Children's Mercy Hospitals and Clinics, Pediatric Research Center, 4th floor, 2401 Gillham Rd, Kansas City, MO 64108, USA. rwhite@cmh.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: White
authors.forename: Steven G
authors.initials: SG
authors.lastname: McNulty
authors.forename: Shelly
authors.initials: S
authors.lastname: Roman
authors.forename: Uttam
authors.initials: U
authors.lastname: Garg
authors.forename: Eric
authors.initials: E
authors.lastname: Wirtz
authors.forename: Deanna
authors.initials: D
authors.lastname: Kohlbrecher
authors.forename: Ndona N
authors.initials: NN
authors.lastname: Nsumu
authors.forename: David
authors.initials: D
authors.lastname: Pinson
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: Krista
authors.initials: K
authors.lastname: Blackmore
authors.forename: Angela
authors.initials: A
authors.lastname: Copple
authors.forename: Sidrah
authors.initials: S
authors.lastname: Rasul
authors.forename: Masayo
authors.initials: M
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D016332:Fetal Tissue Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D019266:Iron, Dietary / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D017086:beta-Thalassemia / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019266:Iron, Dietary