Leukaemia disease genes: Large-scale cloning and pathway predictions Academic Article uri icon


MeSH Major

  • Cloning, Molecular
  • Leukemia, Experimental
  • Oncogenes
  • Signal Transduction


  • Retroviral insertional mutagenesis in BXH2 and AKXD recombinant inbred mice induces a high incidence of myeloid or B- and T-cell leukaemia and the proviral integration sites in the leukaemias provide powerful genetic tags for disease gene identification. Some of the disease genes identified by proviral tagging are also associated with human disease, validating this approach for human disease gene identification. Although many leukaemia disease genes have been identified over the years, many more remain to be cloned. Here we describe an inverse PCR (IPCR) method for proviral tagging that makes use of automated DNA sequencing and the genetic tools provided by the Mouse Genome Project, which increases the throughput for disease gene identification. We also use this IPCR method to clone and analyse more than 400 proviral integration sites from AKXD and BXH2 leukaemias and, in the process, identify more than 90 candidate disease genes. Some of these genes function in pathways already implicated in leukaemia, whereas others are likely to define new disease pathways. Our studies underscore the power of the mouse as a tool for gene discovery and functional genomics.

publication date

  • November 1999



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1038/15531

PubMed ID

  • 10610183

Additional Document Info

start page

  • 348

end page

  • 53


  • 23


  • 3