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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, Y. Articles by D'Andrea, A. D. Search for Related Content PubMed PubMed Citation Articles by Yang, Y. Articles by D'Andrea, A. D. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3435-3440 RED CELLS Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9 Yi Yang, Yanan Kuang, Rocio Montes De Oca, Tobias Hays, Lisa Moreau, Naifang Lu, Brian Seed, and Alan D. D'Andrea From the Department of Molecular Biology, Massachusetts General Hospital; Department of Genetics, Harvard Medical School; Department of Pediatric Oncology, Dana-Farber Cancer Institute; and Department of Pediatrics, Children's Hospital, Harvard Medical School; all of Boston, MA. 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. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B.-Y. Liao and J. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020