In vivo magnetic resonance imaging of transgenic mice expressing human ferritin.

OBJECTIVE: 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. PROCEDURES: 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.
RESULTS: 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).
CONCLUSIONS: 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.