title: The C282Y mutation causing hereditary hemochromatosis does not produce a null allele.
abstract: Targeted mutagenesis was used to produce two mutations in the murine hemochromatosis gene (Hfe) locus. The first mutation deletes a large portion of the coding sequence, generating a null allele. The second mutation introduces a missense mutation (C282Y) into the Hfe locus, but otherwise leaves the gene intact. This mutation is identical to the disease-causing mutation in patients with hereditary hemochromatosis. Mice carrying each of the two mutations were bred and analyzed. Homozygosity for either mutation results in postnatal iron loading. The effects of the null mutation are more severe than the effects of the C282Y mutation. Mice heterozygous for either mutation accumulate more iron than normal controls. Interestingly, although liver iron stores are greatly increased, splenic iron is decreased. We conclude that the C282Y mutation does not result in a null allele.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital, Howard Hughes Medical Institute, Boston, MA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Levy
authors.forename: L K
authors.initials: LK
authors.lastname: Montross
authors.forename: D E
authors.initials: DE
authors.lastname: Cohen
authors.forename: M D
authors.initials: MD
authors.lastname: Fleming
authors.forename: N C
authors.initials: NC
authors.lastname: Andrews
mesh_terms: D000483:Alleles; D000818:Animals; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D020125:Mutation, Missense; D017384:Sequence Deletion
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins