Journal
NMR IN BIOMEDICINE
Volume 23, Issue 5, Pages 523-531Publisher
WILEY-BLACKWELL
DOI: 10.1002/nbm.1491
Keywords
ferritin; reporter gene; iron; aging
Funding
- Minerva Foundation
- European Commission
- European Research Council [232640-IMAGO]
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The iron storage protein, ferritin, provides an important endogenous MRI contrast that can be used to determine the level of tissue iron. In recent years the impact of modulating ferritin expression on MRI contrast and relaxation rates was evaluated by several groups, using genetically modified cells, viral gene transfer and transgenic animals. This paper reports the follow-up of transgenic mice that chronically over-expressed the heavy chain of ferritin (h-ferritin) in liver hepatocytes (liver-hfer mice) over a period of 2 years, with the aim of investigating the long-term effects of elevated level of h-ferritin on MR signal and on the well-being of the mice. Analysis revealed that aging liver-hfer mice, exposed to chronic elevated expression of h-ferritin, have increased R-2 values compared to WT. As expected for ferritin, R2 difference was strongly enhanced at high magnetic field. Histological analysis of these mice did not reveal liver changes with prolonged over expression of ferritin, and no differences could be detected in other organs. Furthermore, dietary iron supplementation significantly affected MRI contrast, without affecting animal wellbeing, for both wildtype and ferritin over expressing transgenic mice. These results suggest the safety of ferritin overexpression, and support the use of h-ferritin as a reporter gene for MRI. Copyright (C) 2010 John Wiley & Sons, Ltd.
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