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Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice.

In this study, mice expressing one of the two Mre11 alleles inherited in the human ataxia-telangiectasia like disorder (A-TLD) were derived. The mutation had a profound maternal effect on embryonic viability, revealing an acute requirement for Mre11 complex function in early embryogenesis. Mre11(ATLD1/ATLD1) mice exhibited several indices of impaired ATM function. The mice also exhibited pronounced chromosomal instability. Despite this phenotypic spectrum, the animals were not prone to malignancy. These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance the initiation of tumorigenesis. In contrast, the latency of malignancy in p53(+/-) mice was dramatically reduced. We propose that in Mre11(ATLD1/ATLD1) mice, genome instability and cell cycle checkpoint defects reduce viability in early embryos and in proliferating cells, while promoting malignancy in the context of an initiating lesion.

Pubmed ID: 14690604


  • Theunissen JW
  • Kaplan MI
  • Hunt PA
  • Williams BR
  • Ferguson DO
  • Alt FW
  • Petrini JH


Molecular cell

Publication Data

December 23, 2003

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI35714
  • Agency: NCI NIH HHS, Id: CA92625
  • Agency: NIGMS NIH HHS, Id: GM59413
  • Agency: NICHD NIH HHS, Id: HD37502
  • Agency: NHLBI NIH HHS, Id: K08 HL67580

Mesh Terms

  • Animals
  • Ataxia Telangiectasia
  • Cell Cycle
  • Cells, Cultured
  • Chromosomal Instability
  • Chromosomes, Mammalian
  • DNA Damage
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Female
  • Fertility
  • Fibroblasts
  • Genes, cdc
  • Humans
  • Karyotyping
  • Lymphoma
  • Mice
  • Pregnancy
  • Survival Rate
  • Tumor Suppressor Protein p53