Contributions of beta 2-microglobulin-dependent molecules and lymphocytes to iron regulation: insights from HfeRag1(-/-) and beta 2mRag1(-/-) double knock-out mice

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Miranda, CJ (Author) Other; Makui, H (Author) Other; Andrews, NC (Author) Other; Santos, MM (Author) REIT

Journal

Title: Blood

Vol. 103

Pages: 2847-2849

ISSN: 0006-4971

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 26 Citations

Other information

Authenticus ID: P-000-AWH

DOI: 10.1182/blood-2003-09-3300

Abstract (EN): 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 We 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. (C) 2004 by The American Society of Hematology.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 3