Simple and Robust Intravital Microscopy Procedures in Hybrid TIE2GFP-BALB/c Transgenic Mice

Mol Imaging Biol. 2020 Jun;22(3):486-493. doi: 10.1007/s11307-019-01442-2.

Abstract

Purpose: The endeavor of deciphering intricate phenomena within the field of molecular medicine dictates the necessity to investigate tumor/disease microenvironment real-time on cellular level. We, hereby, design simple and robust intravital microscopy strategies, which can be used to elucidate cellular or molecular interactions in a fluorescent mouse model.

Procedures: We crossbred transgenic TIE2GFP mice with nude BALB/c mice, allowing the breeding of immunocompetent and immunodeficient mouse models expressing green fluorescent protein (GFP) in vascular endothelium. Then, we surgically exposed various tissues of interest to perform intravital microscopy.

Results: By utilizing simple tissue preparation procedures and confocal or two-photon microscopy, we produced high-resolution static snapshots, dynamic sequences, and 3D reconstructions of orthotopically grown mammary tumor, skin inflammation, brain, and muscle. The homogenous detection of GFP expressed by endothelial cells and a combination of fluorescence agents enabled landmarking of tumor microenvironment and precise molecular tagging.

Conclusion: Simple intravital microscopy procedures on TIE2GFP mice allowed a real-time multi-color visualization of tissue microenvironment, underlining that robust microscopy strategies are relatively simple and can be readily available for many tissues of interest.

Keywords: Confocal microscopy; Fluorescence; Intravital microscopy; Molecular imaging; Multiphoton microscopy; Optical imaging; Transgenic TIE2GFP mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Intravital Microscopy / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Confocal / methods*
  • Receptor, TIE-2 / chemistry
  • Receptor, TIE-2 / genetics*
  • Receptor, TIE-2 / metabolism
  • Tumor Microenvironment

Substances

  • Green Fluorescent Proteins
  • Receptor, TIE-2
  • Tek protein, mouse