Authors: | Vyazunova, I.; Maklakova, V. I.; Berman, S.; De, I.; Steffen, M. D.; Hong, W.; Lincoln, H.; Morrissy, A. S.; Taylor, M. D.; Akagi, K.; Brennan, C. W.; Rodriguez, F. J.; Collier, L. S. |
Article Title: | Sleeping beauty mouse models identify candidate genes involved in gliomagenesis |
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. |
Keywords: | controlled study; promoter region; nonhuman; glioma; protein analysis; mouse; animal tissue; gene; gene expression; glial fibrillary acidic protein; animal experiment; animal model; gene locus; carcinogenesis; molecular cloning; oncogene; tumor suppressor gene; messenger rna; epigenetics; gene identification; glioblastoma; nucleotide sequence; gene insertion; mutagenesis; transposon; crebbp gene; smad4 gene; human; article; abtb2 gene; arid1b gene; chd7 gene; csf1 gene; dyrk1a gene; elovl6 gene; faf1 gene; fli1 gene; gramd1c gene; hepacam2 gene; kpna4 gene; lsamp gene; mir101c gene; mkln1 gene; nav3 gene; nfia gene; pag1 gene; ppp3r1 gene; rbpj gene; rps6ka5 gene; tanc2 gene; tsg101 gene; usp9x gene; zfp212 gene |
Journal Title: | PLoS ONE |
Volume: | 9 |
Issue: | 11 |
ISSN: | 1932-6203 |
Publisher: | Public Library of Science |
Date Published: | 2014-11-25 |
Start Page: | e113489 |
Language: | English |
DOI: | 10.1371/journal.pone.0113489 |
PROVIDER: | scopus |
PMCID: | PMC4244117 |
PUBMED: | 25423036 |
DOI/URL: | |
Notes: | Export Date: 2 January 2015 -- Source: Scopus |