MRI detection of transcriptional regulation of gene expression in transgenic mice

Nat Med. 2007 Apr;13(4):498-503. doi: 10.1038/nm1497. Epub 2007 Mar 11.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Embryo, Mammalian / metabolism
  • Endothelial Cells / metabolism
  • Ferritins / genetics
  • Ferritins / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hepatocytes / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Tetracycline / metabolism
  • Tetracycline / pharmacology

Substances

  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Ferritins
  • Tetracycline

Associated data

  • GENBANK/NM010239