Comparative study between Hfe-/- and beta2m-/- mice: progression with age of iron status and liver pathology.
Hepatic iron overload in hemochomatosis patients can be highly variable but in general it develops in older patients. The purpose of this study was to compare development of iron load in of beta2m-/- and Hfe-/- mice paying special attention to liver pathology in older age groups. Liver iron content of beta2m-/-, Hfe-/- and control B6 mice of different ages (varying from 3 weeks to 18 months) was examined. Additional parameters (haematology indices, histopathology, lipid content and ferritin expression) were also studied in 18-month-old mice. The beta2m-/- strain presents higher hepatic iron content, hepatocyte nuclear iron inclusions, mitochondria abnormalities. In addition, hepatic steatosis was a common observation in this strain. In the liver of Hfe-/- mice, large mononuclear infiltrates positive for ferritin staining were commonly observed. The steatosis commonly observed the beta2m-/- mice may be a reflection of its higher hepatic iron content. The large hepatic mononuclear cell infiltrates seen in Hfe-/- stained for ferritin, may point to the iron sequestration capacity of lymphocytes and contribute to the clarification of the differences found in the progression of hepatic iron overload and steatosis in older animals from the two strains.
Rodrigues
Pedro
P
Iron Genes and Immune System (IRIS), Institute for Molecular and Cell Biology (IBMC), Porto, Portugal. prodrigu@ibmc.up.pt
Lopes
Célia
C
Mascarenhas
Claudia
C
Arosio
Paolo
P
Porto
Graça
G
De Sousa
Maria
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D018450:Disease Progression; D005293:Ferritins / Q000032:analysis; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D014168:Transferrin / Q000032:analysis; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D001613:beta 2-Microglobulin; D005293:Ferritins; D007501:Iron