Intestinal iron absorption studies in mouse models of iron-overload.
Three mouse strains have been evaluated as suitable models for investigations into the pathogenesis of iron-overload syndromes. Mice with hereditary heterozygous alpha-thalassaemia had moderately raised reticulocyte counts, but were not anaemic and showed little, if any, iron loading. In contrast, mice with homozygous beta-thalassaemia showed microcytic anaemia, reticulocytosis and splenomegaly. Iron-loading was marked, progressive with age and mainly confined to the spleen. Liver iron-loading increased until the age of 7-8 weeks, with no further increase over successive weeks. Although intestinal iron absorption was modestly increased due to enhanced mucosal uptake, the majority of the 'excess' liver and spleen iron could be accounted for by re-distribution of iron from the erythrocytic compartment. Homozygous hypotransferrinaemic mice, with approximately 1-2% of normal plasma transferrin levels, were markedly anaemic with hypochromic microcytic erythrocytes. Intestinal iron absorption increased 3-4-fold (predominantly due to changes in mucosal transfer), as compared to wild-type controls and heterozygotes, and was ascertained to be a major factor causing the marked hepatic iron overload. Heterozygous hypotransferrinamic mice, with over half normal plasma transferrin levels and a mild degree of hepatic iron loading, showed very similar characteristics to wild-type controls. Thus, of the three models, hpx/hpx mice showed the greatest enhancement in intestinal iron absorption and net iron-loading and provides a suitable animal model of spontaneous iron-overload. Comparison of iron absorption values between the models suggests that reticulocytes cannot account for the enhanced absorption seen in the hpx/hpx mice.
Raja
K B
KB
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London.
Simpson
R J
RJ
Peters
T J
TJ
D000818:Animals; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013789:Thalassemia / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D017085:alpha-Thalassemia / Q000097:blood / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000378:metabolism
D014168:Transferrin; D007501:Iron