Contributions of beta2-microglobulin-dependent molecules and lymphocytes to iron regulation: insights from HfeRag1(-/-) and beta2mRag1(-/-) double knock-out mice.

Journal Article (Journal Article)

Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE gene, coding for a beta2-microglobulin (beta2m)-associated major histocompatibility complex class I-like protein. However, iron accumulation in patients with HH can be highly variable. Previously, analysis of beta2mRag1(-/-) double-deficient mice, lacking all beta2m-dependent molecules and lymphocytes, demonstrated increased iron accumulation in the pancreas and heart compared with beta2m single knock-out mice. To evaluate whether the observed phenotype in beta2mRag1(-/-) mice was due solely to the absence of Hfe or to other beta2m-dependent molecules, we generated HfeRag1(-/-) double-deficient mice. Our studies revealed that introduction of Rag1 deficiency in Hfe knock-out mice leads to heightened iron overload, mainly in the liver, whereas the heart and pancreas are relatively spared compared with beta2mRag1(-/-) mice. These results suggest that other beta2m-interacting protein(s) may be involved in iron regulation and that in the absence of functional Hfe molecules lymphocyte numbers may influence iron overload severity.

Full Text

Duke Authors

Cited Authors

  • Miranda, CJ; Makui, H; Andrews, NC; Santos, MM

Published Date

  • April 1, 2004

Published In

Volume / Issue

  • 103 / 7

Start / End Page

  • 2847 - 2849

PubMed ID

  • 14656877

Pubmed Central ID

  • PMC2891006

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2003-09-3300


  • eng

Conference Location

  • United States