Sleeping beauty mouse models identify candidate genes involved in gliomagenesis

Irina Vyazunova, Vilena I. Maklakova, Samuel Berman, Ishani De, Megan D. Steffen, Won Hong, Hayley Lincoln, A. Sorana Morrissy, Michael D. Taylor, Keiko Akagi, Cameron W. Brennan, Fausto J. Rodriguez, Lara S. Collier

Research output: Contribution to journalArticlepeer-review

Abstract

Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.

Original languageEnglish (US)
Article numbere113489
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 25 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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