ArticleProceedings of the National Academy of Sciences of the United States of America2001
Naturally variant autosomal and sex-linked loci determine the severity of iron overload in beta 2-microglobulin-deficient mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 43 citations in OpenAlex.
- Pathological frataxin deficiency in mice causes tissue-specific alterations in iron homeostasis.iScience · 2026Article
- Cerebrospinal fluid β2-microglobulin promotes the tau pathology through microglia-astrocyte communication in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Repercussion of SARS-CoV-2 on the Sexual Function in Males: An Updated Review.Infectious disorders drug targets · 2025Review
- Anti-Thyroid Peroxidase Antibodies and Male Gender Are Associated with Diabetes Occurrence in Patients with Beta-Thalassemia Major.Journal of diabetes research · 2016Article
- Gender-related variations in iron metabolism and liver diseases.World journal of hepatology · 2010Article
- A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis.British journal of haematology · 2009Article
- Function of the hemochromatosis protein HFE: Lessons from animal models.World journal of gastroenterology · 2008Article
- Forging a field: the golden age of iron biology.Blood · 2008Review
- The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading.Blood · 2005Article
- Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- The haemochromatosis protein HFE induces an apparent iron-deficient phenotype in H1299 cells that is not corrected by co-expression of beta 2-microglobulin.The Biochemical journal · 2003Article
- Iron status in mice carrying a targeted disruption of lactoferrin.Molecular and cellular biology · 2003Article
- Mapping genes responsible for strain-specific iron phenotypes in murine chromosome substitution strains.Blood cells, molecules & diseasesArticle
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue gene HFE has been found to be a primary cause of HH. However, many individuals homozygous for the defective allele of HFE do not develop iron overload, raising the possibility that genetic variation in modifier loci contributes to the HH phenotype. Mice deficient in the product of the beta(2)-microglobulin (beta(2)M) class I light chain fail to express HFE and other MHC class I family proteins, and they have been found to manifest many characteristics of the HH phenotype. To determine whether natural genetic variation plays a role in controlling iron overload, we performed classical genetic analysis of the iron-loading phenotype in beta(2)M-deficient mice in the context of different genetic backgrounds. Strain background was found to be a major determinant in iron loading. Sex played a role that was less than that of strain background but still significant. Resistance and susceptibility to iron overload segregated as complex genetic traits in F(1) and back-cross progeny. These results suggest the existence of naturally variant autosomal and Y chromosome-linked modifier loci that, in the context of mice genetically predisposed by virtue of a beta(2)M deficiency, can profoundly influence the severity of iron loading. These results thus provide a genetic explanation for some of the variability of the HH phenotype.
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