Evaluation of ferritin-overexpressing brain in newly developed transgenic mice.
Aberrant expression of ferritin, a major iron-binding protein, has shown to be involved in neurodegenerative diseases. In this study, we generated transgenic (Tg) mice of human ferritin heavy chain (FTH) gene and investigated the effects of ferritin overexpression in FTH-Tg brain by (1)H-MRI and (1)H-MRS. The mice displayed no apparent neurological symptoms, and no specific morphological and T(2) alterations were found in the brain by MRI, and not even by histological studies. (1)H-MRS, however, revealed that some metabolic markers were significantly altered in FTH-Tg brains compared to wild-type control brains, such as decreases in myo-inositol and glutamine, and an increase in lactate. Our present studies suggested that despite the absence of neurological, morphological, T(2), and histological signatures, brain metabolisms were significantly affected in FTH-Tg mice. This study also highlights the usefulness of (1)H-MRS in the analysis of transgenic mouse models.
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. shase@nirs.go.jp
Sumitaka
S
Hasegawa
Shigeyoshi
S
Saito
Jun-ichi
J
Takanashi
Yukie
Y
Morokoshi
Takako
T
Furukawa
Tsuneo
T
Saga
Ichio
I
Aoki
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
D005293:Ferritins