Iron metabolism in transgenic mice with hypoplastic anaemia due to incomplete deficiency of erythropoietin.
Iron overload is a serious complication of many forms of anaemia, arising in part from mechanisms associated with compensatory increases in erythropoiesis. To investigate other mechanisms by which anaemia itself may perturb iron metabolism, without the confounding effects of compensatory erythropoiesis, we studied transgenic mice with a partially disabling insertion in the erythropoietin gene, which manifested as incomplete erythropoietin deficiency. Mice were studied aged 7-8 weeks. Haemoglobin concentrations were 6.6 +/- 0.8 g/dl in mice homozygous for the modified erythropoietin gene, 12.9 +/- 2.2 g/dl in heterozygous mice and 14.1 +/- 1.0 g/dl in controls. Homozygous mice showed significant hepatic iron loading (2-fold increase in liver non-haem iron, compared with heterozygous mice and normal controls, with iron staining principally in the periportal hepatocytes). Absorption studies using 59Fe showed increased uptake from the lumen of an in vivo isolated duodenal segment in homozygous mice, although at this point in time overall transfer of radioiron to the circulation and other tissues (mucosal transfer) was not different from controls. These observations demonstrate that anaemia can lead to hepatic iron loading even in the absence of increased erythropoiesis, and are consistent with the possibility that anaemic hypoxia can enhance mucosal iron uptake by the duodenal enterocyte.
Raja
K B
KB
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London.
Maxwell
P H
PH
Ratcliffe
P J
PJ
Salisbury
J R
JR
Simpson
R J
RJ
Peters
T J
TJ
D000042:Absorption; D000741:Anemia, Aplastic / Q000097:blood / Q000378:metabolism*; D000818:Animals; D004921:Erythropoietin / Q000097:blood / Q000172:deficiency*; D005293:Ferritins / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic
D004921:Erythropoietin; D005293:Ferritins; D007501:Iron