PMID- 8643666
OWN - NLM
STAT- MEDLINE
DCOM- 19960717
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 93
IP  - 4
DP  - 1996 Feb 20
TI  - beta2 knockout mice develop parenchymal iron overload: A putative role for class 
      I genes of the major histocompatibility complex in iron metabolism.
PG  - 1529-34
AB  - Hemochromatosis (HC) is an inherited disorder of iron absorption, mapping within 
      the human major histocompatibility complex (MHC). We have identified a multigene 
      system in the murine MHC that contains excellent candidates for the murine 
      equivalent of the human HC locus and implicate nonclassical class I genes in the 
      control of iron absorption. This gene system is characterized by multiple copies 
      of two head-to-head genes encoded on opposite strands and driven by one common 
      regulatory motif. This regulatory motif has a striking homology to the promoter 
      region of the beta-globin gene, a gene obviously involved in iron metabolism and 
      hence termed beta-globin analogous promoter (betaGAP). Upstream of the betaGAP 
      sequence are nonclassical class I genes. At least one of these nonclassical class 
      I genes, Q2, is expressed in the gastrointestinal tract, the primary site of iron 
      absorption. Also expressed in the gastrointestinal tract and downstream of the 
      betaGAP motif is a second set of putative genes, termed Hephaestus (HEPH). Based 
      on these observations, we hypothesized that the genes that seem to be controlled 
      by the betaGAP regulatory motifs would be responsible for the control of Fe 
      absorption. As a test of this hypothesis, we predicted that mice which have 
      altered expression of class I gene products, the beta2-microglobulin knockout 
      mice, [beta2m(-/-)], would develop Fe overload. This prediction was confirmed, 
      and these results indicate beta2m-associated proteins are involved in the control 
      of intestinal Fe absorption.
FAU - Rothenberg, B E
AU  - Rothenberg BE
AD  - Department of Medicine, University of California at San Diego, La Jolla, 
      92093-0634, USA.
FAU - Voland, J R
AU  - Voland JR
LA  - eng
GR  - AI-23287/AI/NIAID NIH HHS/United States
GR  - AI-31870/AI/NIAID NIH HHS/United States
GR  - AI-33204/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (beta 2-Microglobulin)
RN  - 9004-22-2 (Globins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - *Disease Models, Animal
MH  - Gene Expression Regulation
MH  - *Genes, MHC Class I
MH  - Genetic Linkage
MH  - Globins/genetics
MH  - Hemochromatosis/*genetics/metabolism/physiopathology
MH  - Intestinal Absorption/*genetics
MH  - Iron/*pharmacokinetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Regulatory Sequences, Nucleic Acid
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - beta 2-Microglobulin/deficiency/*genetics
PMC - PMC39974
EDAT- 1996/02/20 00:00
MHDA- 1996/02/20 00:01
PMCR- 1996/08/20
CRDT- 1996/02/20 00:00
PHST- 1996/02/20 00:00 [pubmed]
PHST- 1996/02/20 00:01 [medline]
PHST- 1996/02/20 00:00 [entrez]
PHST- 1996/08/20 00:00 [pmc-release]
AID - 10.1073/pnas.93.4.1529 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1529-34. doi: 10.1073/pnas.93.4.1529.