• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc(-/-) and Fanca(-/-) mice, the Fancg(-/-) mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from the Fancg(-/-) mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg(-/-) lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubiquitination of the downstream Fancd2 protein in response to IR. Finally, Fancg(-/-) mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of the Fancg gene confirms the role of Fancg in the FA pathway. The Fancg(-/-) mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies.

Pubmed ID: 11719385

Authors

  • Yang Y
  • Kuang Y
  • Montes De Oca R
  • Hays T
  • Moreau L
  • Lu N
  • Seed B
  • D'Andrea AD

Journal

Blood

Publication Data

December 1, 2001

Associated Grants

  • Agency: NHLBI NIH HHS, Id: P01-HL54785-04
  • Agency: NIAID NIH HHS, Id: R01-AI27849
  • Agency: NIDDK NIH HHS, Id: R01-DK43889-09
  • Agency: NHLBI NIH HHS, Id: R01-HL52725-04
  • Agency: NHLBI NIH HHS, Id: UO1-HL66678

Mesh Terms

  • Alleles
  • Animals
  • Chromosome Breakage
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Fanconi Anemia
  • Fanconi Anemia Complementation Group G Protein
  • Hematopoietic Stem Cells
  • Homozygote
  • Humans
  • Immunoblotting
  • Infertility
  • Mice
  • Mice, Knockout
  • Mitomycin
  • Mutagenesis
  • Phenotype
  • Spleen