MRI detection of transcriptional regulation of gene expression in transgenic mice.
Ferritin, the iron storage protein, was recently suggested to be a candidate reporter for the detection of gene expression by magnetic resonance imaging (MRI). Here we report the generation of TET:EGFP-HAferritin (tet-hfer) transgenic mice, in which tissue-specific inducible transcriptional regulation of expression of the heavy chain of ferritin could be detected in vivo by MRI. We show organ specificity by mating the tet-hfer mice with transgenic mice expressing tetracycline transactivator (tTA) in liver hepatocytes and in vascular endothelial cells. Tetracycline-regulated overexpression of ferritin resulted in specific alterations of the transverse relaxation rate (R(2)) of water. Transgene-dependent changes in R(2) were detectable by MRI in adult mice, and we also found fetal developmental induction of transgene expression in utero. Thus, the tet-hfer MRI reporter mice provide a new transgenic mouse platform for in vivo molecular imaging of reporter gene expression by MRI during both embryonic and adult life.
Cohen
Batya
B
Department of Biological Regulation, Weizmann Institute, Rehovot 76100, Israel.
Ziv
Keren
K
Plaks
Vicki
V
Israely
Tomer
T
Kalchenko
Vyacheslav
V
Harmelin
Alon
A
Benjamin
Laura E
LE
Neeman
Michal
M
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004622:Embryo, Mammalian / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013752:Tetracycline / Q000378:metabolism / Q000494:pharmacology
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005293:Ferritins; D013752:Tetracycline