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

Blood | Dec 1, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11719385

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 RIS Download

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

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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

Mouse Genome Informatics (Data, Gene Annotation)

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