Back to Search
Start Over
Long-term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis
- Source :
- European Journal of Clinical Investigation. 32:603-612
- Publication Year :
- 2002
- Publisher :
- Wiley, 2002.
-
Abstract
- Background HFE knockout mice (C57BL/6 x 129/Ola strain) mimic the functional aberrations of human hereditary haemochromatosis (HH) in short-term experiments. The present study investigates functional and morphological long-term changes. Methods HFE(o/o), HFE(+/o) and HFE(+/+) mice were maintained on iron-rich and control diets for 2 weeks, 3, 12 and 18 months. Light microscopic tissue iron distribution, pathomorphological alterations, tissue iron content and oxidative stress were analysed in liver, pancreas, spleen, gastrointestinal tract, kidneys and myocardium. Additionally, duodenal 59Fe absorption and 59Fe whole body loss were measured. Results Iron distribution between organs and microscopic iron deposition in the tissues resembled the patterns described in HH. After 3 months of iron-rich feeding duodenal 59Fe absorption decreased to approximately 15% of iron-adequate controls but remained about twice as high in HFE(o/o) as in HFE(+/+) mice. Hepatic iron concentrations reached only half the values known to induce hepatic fibrosis in rats and humans, while whole body 59Fe loss was about twice as high. Consequently no hepatic fibrosis developed, although massive hepatocellular iron deposition and indication for oxidative stress were observed. Conclusion C57BL/6 x 129/O1a HFE(o/o) mice mimic HH iron distribution and the regulation of intestinal iron absorption after long-term feeding. However, characteristic morphological late changes in untreated HH are not modelled.
- Subjects :
- C57BL/6
medicine.medical_specialty
Gastrointestinal tract
biology
Clinical Biochemistry
Spleen
General Medicine
medicine.disease
biology.organism_classification
medicine.disease_cause
Biochemistry
Intestinal absorption
medicine.anatomical_structure
Endocrinology
Internal medicine
Knockout mouse
medicine
Hepatic fibrosis
Hemochromatosis
Oxidative stress
Subjects
Details
- ISSN :
- 00142972
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- European Journal of Clinical Investigation
- Accession number :
- edsair.doi...........f4836c0b1da4462829c78489cccab688