| First Author | Yang Y | Year | 2001 |
| Journal | Blood | Volume | 98 |
| Issue | 12 | Pages | 3435-40 |
| PubMed ID | 11719385 | Mgi Jnum | J:72945 |
| Mgi Id | MGI:2154029 | Doi | 10.1182/blood.v98.12.3435 |
| Citation | Yang Y, et al. (2001) Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9. Blood 98(12):3435-40 |
| abstractText | 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. |
