The response of Parp knockout mice against DNA damaging agents

Mutat Res. 2000 Apr;462(2-3):159-66. doi: 10.1016/s1383-5742(00)00033-8.


Gene-disruption studies involving poly(ADP-ribose) polymerase (Parp) have identified the various roles of Parp in cellular responses to DNA damage. The partial rescue of V[D]J recombination process in SCID/Parp(-/-) double mutant mice indicates the participation of Parp in the repair of DNA strand break. Parp(-/-) mice are more sensitive to the lethal effects of alkylating agents. Parp is also thought to be involved in base-excision repair after DNA damage caused by alkylating agents. On the other hand, resistance of Parp(-/-) mice to DNA damage induced by reactive oxygen species implicates the contribution of Parp to cell death through NAD depletion. Parp(-/-) mice with two different genetic backgrounds also show enhanced sensitivity to the lethal effects of gamma-irradiation. Parp(-/-) mice show more severe villous atrophy of the small intestine compared to the wild-type counterpart in a genetic background of 129Sv/C57BL6. Other forms of enhanced tissue damage have been identified in Parp(-/-) mice with a genetic background of 129Sv/ICR. For example, Parp(-/-) mice exhibit extensive hemorrhage in the glandular stomach and other tissues, such as the testes, after gamma-irradiation. Severe myelosuppression is also observed in both Parp(+/+) and Parp(-/-) mice, but Parp(+/+) mice show extensive extramedullary hematopoiesis in the spleen during the recovery phase of post-irradiation, whereas the spleen of Parp(-/-) mice exhibits severe atrophy with no extramedullary hematopoiesis. The absence of extramedullary hematopoiesis in the spleen is probably the underlying mechanism of hemorrhagic tendency in various tissues of Parp(-/-) mice. These findings suggest that loss of Parp activity could contribute to post-irradiation tissue hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / administration & dosage*
  • Animals
  • Cell Death
  • DNA / drug effects*
  • DNA / genetics
  • DNA Damage*
  • DNA Repair
  • Gastric Mucosa / metabolism
  • Male
  • Methyl Methanesulfonate / administration & dosage
  • Methylnitrosourea / administration & dosage
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, SCID
  • Mutation
  • NAD / metabolism
  • Poly(ADP-ribose) Polymerases / genetics*
  • Poly(ADP-ribose) Polymerases / physiology
  • Spleen / metabolism
  • Spleen / pathology
  • Spleen / radiation effects
  • Stomach / pathology
  • Stomach / radiation effects
  • Survival Analysis
  • Testis / metabolism
  • Testis / pathology
  • Testis / radiation effects


  • Alkylating Agents
  • NAD
  • Methylnitrosourea
  • DNA
  • Methyl Methanesulfonate
  • Poly(ADP-ribose) Polymerases