title: Mapping genes responsible for strain-specific iron phenotypes in murine chromosome substitution strains.
abstract: The highly variable clinical phenotype observed in patients homozygous for the C282Y mutation of the hereditary hemochromatosis gene (HFE) is likely due to the influence of non-HFE modifier genes. The primary functional abnormality causing iron overload in hemochromatosis is hyper-absorption of dietary iron. We found that iron absorption in inbred mice varies in a strain-specific manner, as does the pattern of iron distribution to the liver and spleen. A/J mice absorbed approximately twice the amount of 59Fe delivered by gavage compared to the C57BL/6 strain. Genetic comparisons between A/J and C57BL/6 were facilitated by the availability of consomic chromosome substitution strains (CSS). Each CSS has an individual chromosome pair from A/J on an otherwise C57BL/6J background. We found that iron absorption and iron content in liver and in spleen were continuous variables suggesting that each trait is under multigenic control. No trait co-segregated among the CSS. Chromosome 5 from A/J, however, imparted the highest iron absorption phenotype and multiple CSS had absorption levels equivalent to A/J. Chromosomes 9 and X were associated with high spleen iron content. These data suggest that multiple genes contribute to the regulation of iron absorption and that individual organ iron phenotypes are independently regulated.
authors.affiliation: Division of Hematology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. richard.ajioka@hsc.utah.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Ajioka
authors.forename: Renee C
authors.initials: RC
authors.lastname: LeBoeuf
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Gillespie
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Amon
authors.forename: James P
authors.initials: JP
authors.lastname: Kushner
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D040582:Inheritance Patterns; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D013154:Spleen / Q000737:chemistry
chemical_list: D007501:Iron