In Vivo Magnetic Resonance Imaging of Transgenic Mice Expressing Human Ferritin

Abstract

This study aims to produce the transgenic mice (TG) engineered for magnetic resonance imaging (MRI) studies based on the ubiquitous expression of ferritin MRI reporter gene in diverse tissues. Transgenic mice (TG) expressing myc-tagged human heavy chain ferritin (myc-hFTH) under the control of a ubiquitous CAG promoter were produced. The expression of myc-hFTH in diverse tissues of the myc-hFTH TG was assessed by RT-PCR, Western blotting, and immunohistochemistry. The iron accumulation and the deposition of ferritin aggregates in tissues of myc-hFTH TG and WT were analyzed by Prussian blue staining and transmission electron microscopy. The myc-hFTH TG (n = 9) and wild-type mice (WT) (n = 4) were subjected to MRI on 9.4 T MR scanner. An eight-point T(2)* mapping was performed using a multiple gradient echo sequence, and T(2)* value was estimated pixel by pixel by using a routine least-squares fitting algorithm. We generated the myc-hFTH TG expressing myc-hFTH in brain, heart, liver, lung, spleen, pancreas, kidney, and intestine. The myc-hFTH TG showed no apparent pathological symptoms and no histological changes compared to WT. The expression of myc-hFTH in the brain and liver tissues of myc-hFTH TG led to a significant decrease in T(2)* values, as shown by noninvasive MRI, compared to WT (P < 0.05, TG vs. WT). This study demonstrates that the novel myc-hFTH TG, which expresses an MRI reporter in many tissues, would be a valuable animal model of FTH-based molecular imaging in which to study potential therapies for cell and tissue grafting using an MRI technique. These mice could also serve to study disease related with iron metabolism.