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Overexpression of the Fanconi Anemia Group C Gene (FAC) Protects Hematopoietic Progenitors from Death Induced by Fas-mediated Apoptosis¹

Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892 [J. W., T. O., S. K., M. D., J. Y., D. D., J. M. L.]; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 [H. Y.]; Free University of Amsterdam, NL-1081-BT the Netherlands [J. L. T. F.]; and Hematology-Oncology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115 [Y. L.]

Fanconi anemia is a rare, inherited disorder characterized by bone marrow failure, congenital malformations, and cancer susceptibility. The group C Fanconi anemia gene, FAC, identified by expression cloning methods, encodes a protein of unknown function that may be involved in the response to apoptotic stimuli. Hematopoietic progenitor cells from Fac knock-out mice are hypersensitive to IFN-, a molecule that can induce apoptosis through up-regulation of the Fas death receptor. In this study, we used FAC-overexpressing transgenic mice to examine the relationship between FAC and Fas-triggered cell death. Hematopoietic progenitors from FAC-transgenic mice were up to 10-fold less sensitive to the cytolytic effect of Fas-ligation. Our experiments implicate FAC in the regulation of apoptosis mediated by the Fas death receptor.

¹ This work was supported in part by NIH Grant HL52138 (to H. Y.) and a Grant from the March of Dimes Birth Defects Foundation (to H. Y.).

² To whom requests for reprints should be addressed, at NIH, NHLBI, Hematology Branch, 10/ACRF/7C103, Bethesda, MD 20892. Phone: (301) 496-5093; Fax: (301) 496-8396; E-mail: LiuJ@gwgate.nhlbi.nih.gov.

Received 4/21/98. Accepted 6/24/98.

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