title: MRI detection of transcriptional regulation of gene expression in transgenic mice.
abstract: 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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute, Rehovot 76100, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Cohen
authors.forename: Keren
authors.initials: K
authors.lastname: Ziv
authors.forename: Vicki
authors.initials: V
authors.lastname: Plaks
authors.forename: Tomer
authors.initials: T
authors.lastname: Israely
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Kalchenko
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.forename: Laura E
authors.initials: LE
authors.lastname: Benjamin
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
mesh_terms: 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
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005293:Ferritins; D013752:Tetracycline