Tumor suppressor gene identification using retroviral insertional mutagenesis in Blm-deficient mice

Takeshi Suzuki, Ken Ichi Minehata, Keiko Akagi, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

Retroviral insertional mutagenesis preferentially identifies oncogenes rather than tumor suppressor (TS) genes, presumably because a single retroviral-induced mutation is sufficient to activate an oncogene and initiate a tumor, whereas two mutations are needed to inactivate a TS gene. Here we show that TS genes can be identified by insertional mutagenesis when the screens are performed in Blm-deficient backgrounds. Blm-deficient mice, like Bloom syndrome patients, have increased frequencies of mitotic recombination owing to a mutation in the RecQ protein-like-3 helicase gene. This increased mitotic recombination increases the likelihood that an insertional mutation in one allele of a TS gene will become homozygoused by non-sister chromatid exchange and the homozygosity of the insertion provides a marker for identifying the TS gene. We also show that known as well as novel TS genes can be identified by insertional mutagenesis in Blm-deficient mice and identify two JmjC family proteins that contribute to genome stability in species as evolutionarily diverse as mammals and Caenorhabditis elegans.

Original languageEnglish (US)
Pages (from-to)3422-3431
Number of pages10
JournalEMBO Journal
Volume25
Issue number14
DOIs
StatePublished - Jul 26 2006

Keywords

  • Bloom syndrome
  • Insertional mutagenesis
  • Lymphoma
  • Retrovirus
  • Tumor suppressor genes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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