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Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia.

Fanconi anaemia (FA) is an autosomal recessive disease characterized by bone marrow failure, variable congenital malformations and predisposition to malignancies. Cells derived from FA patients show elevated levels of chromosomal breakage and an increased sensitivity to bifunctional alkylating agents such as mitomycin C (MMC) and diepoxybutane (DEB). Five complementation groups have been identified by somatic cell methods, and we have cloned the gene defective in group C (FAC)(7). To understand the in vivo role of this gene, we have disrupted murine Fac and generated mice homozygous for the targeted allele. The -/- mice did not exhibit developmental abnormalities nor haematologic defects up to 9 months of age. However, their spleen cells had dramatically increased numbers of chromosomal aberrations in response to MMC and DEB. Homozygous male and female mice also had compromised gametogenesis, leading to markedly impaired fertility, a characteristic of FA patients. Thus, inactivation of Fac replicates some of the features of the human disease.

Pubmed ID: 8630504


  • Chen M
  • Tomkins DJ
  • Auerbach W
  • McKerlie C
  • Youssoufian H
  • Liu L
  • Gan O
  • Carreau M
  • Auerbach A
  • Groves T
  • Guidos CJ
  • Freedman MH
  • Cross J
  • Percy DH
  • Dick JE
  • Joyner AL
  • Buchwald M


Nature genetics

Publication Data

April 3, 1996

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL52138

Mesh Terms

  • Animals
  • Cloning, Molecular
  • Fanconi Anemia
  • Female
  • Gene Targeting
  • Genes, Recessive
  • Genetic Vectors
  • Homozygote
  • Infertility
  • Male
  • Mice
  • Mutation
  • Ovary
  • Testis