title: Tissue iron loading and histopathological changes in hypotransferrinaemic mice.
abstract: Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
authors.affiliation: Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, U.K.
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: A M
authors.initials: AM
authors.lastname: Konijn
authors.forename: M
authors.initials: M
authors.lastname: Lombard
authors.forename: K B
authors.initials: KB
authors.lastname: Raja
authors.forename: J R
authors.initials: JR
authors.lastname: Salisbury
authors.forename: T J
authors.initials: TJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010179:Pancreas / Q000473:pathology; D012098:Reproduction / Q000502:physiology; D013154:Spleen / Q000473:pathology; D014018:Tissue Distribution; D014168:Transferrin / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D014168:Transferrin; D007501:Iron; D001219:Aspartate Aminotransferases