Modeling Gliomas Using Two Recombinases

Cancer Res. 2019 Aug 1;79(15):3983-3991. doi: 10.1158/0008-5472.CAN-19-0717. Epub 2019 Jul 17.

Abstract

Development of animal models to investigate the complex ecosystem of malignant gliomas using the Cre/loxP recombination system has significantly contributed to our understanding of the molecular underpinnings of this deadly disease. In these model systems, once the tumor is induced by activation of Cre-recombinase in a tissue-specific manner, further genetic manipulations to explore the progression of tumorigenesis are limited. To expand the application of mouse models for gliomas, we developed glial fibrillary acidic protein (GFAP)-FLP recombinase (FLPo) mice that express FLPo recombinase specifically in GFAP-positive cells. Lentivirus-based in vivo delivery of cancer genes conditioned by FLP/FRT-mediated recombination initiated gliomas in GFAP-FLPo mice. Using the Cre-mediated multifluorescent protein-expressing system, we demonstrated that the GFAP-FLPo mouse model enables the analysis of various stages of gliomagenesis. Collectively, we present a new mouse model that will expand our ability to dissect developmental processes of gliomagenesis and to provide new avenues for therapeutic approaches. SIGNIFICANCE: This study presents a new glioma mouse model derived using lentiviral vectors and two recombination systems that will expand the ability to dissect developmental processes of gliomagenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Genotyping Techniques
  • Glioma / genetics*
  • Humans
  • Mice
  • Mice, Transgenic
  • Recombinases / genetics*

Substances

  • Recombinases