Ferritin as a reporter gene for MRI: chronic liver over expression of H-ferritin during dietary iron supplementation and aging.
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, R(2) 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 over-expression, and support the use of h-ferritin as a reporter gene for MRI.
Ziv
Keren
K
Department of Biological Regulation Weizmann Institute of Science, Israel.
Meir
Gila
G
Harmelin
Alon
A
Shimoni
Eyal
E
Klein
Eugenia
E
Neeman
Michal
M
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001052:Apoferritins / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements; D017930:Genes, Reporter / Q000235:genetics*; D006485:Hemosiderin / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007501:Iron / Q000378:metabolism; D019266:Iron, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D013194:Staining and Labeling
D019266:Iron, Dietary; D006485:Hemosiderin; D001052:Apoferritins; D007501:Iron