Chromosome instability and tumor predisposition inversely correlate with BLM protein levels

Lisa D. McDaniel, Nicholas Chester, Mark Watson, Alexander D Borowsky, Philip Leder, Roger A. Schultz

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Independent mouse models for Bloom syndrome (BS) exist, each thought to disrupt Blm gene function. However, animals bearing these alleles exhibit distinct phenotypes. Blmtm1Ches and Blmtm1Grdn homozygous mutant animals exhibit embryonic lethality while in another, Blm tm3Brd, homozygosity yields viable, fertile animals with a cancer predisposition. Further characterization reveals the Blmtm3Brd allele to be a hypomorph, producing a diminished quantity of normal mRNA and protein. The Blmtm3Brd allele produces sufficient normal protein to rescue Blmtm1Ches lethality. Evaluation of viable animals reveals an inverse correlation between the quantity of Blm protein and the level of chromosome instability and a similar genotypic relationship for tumor predisposition indicating that Blm protein is rate limiting for maintaining genomic stability and the avoidance of tumors.

Original languageEnglish (US)
Pages (from-to)1387-1404
Number of pages18
JournalDNA Repair
Issue number12
StatePublished - Dec 9 2003


  • Blm protein
  • Bloom syndrome
  • Cancer
  • Chromosome instability
  • Hypomorph

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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