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Article
Nature Medicine  2, 80 - 86 (1996)
doi:10.1038/nm0196-80

Bcl−2 protects from lethal hepatic apoptosis induced by an ant−Fas antibody in mice

Virginie Lacronique1, Alexandre Mignon1, 2, Monique Fabre3, Benoit Viollet1, Nicolas Rouquet4, Thierry Molina4, Arlette Porteu1, Alexandra Henrion1, Dldier Bouscary5, Paule Varlet5, Virginie Joulin4 & Axel Kahn1

  1Institut Cochin de Géné Moléculaire, U 129 INSERM, Université Rene Descartes, 24 rue du Faubourg Saint Jacques, 75014 Paris, France

  2Service de Réanimation Médicale, CHU Cochin, 75014 Paris, France

  3Service d'Anatomie et de Cytologie Pathologiques, CHU Bicé 78 rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France

  4Institut Cochin de Géné Moléculaire, U 380 INSERM, Université René Descartes, 22 rue Mechain, 75014 Paris, France

  5Institut Cochin de Génétique Moléculaire, U 363 INSERM, Université René Descartes, 27 rue du Faubourg Saint Jacques, 75014 Paris, France

 Correspondence should be addressed to A.K.

Fas is an apoptosis−signaling cell surface antigen that has been shown to trigger cell death upon specific ligand or antibody binding. Treatment of mice with an anti−Fas antibody causes fulminant hepatic failure due to massive apoptosis. To test a putative protective effect of the anti−apoptotic Bcl−2 protein, transgenic mice were generated to express the human bcl−2 gene product in hepatocytes. Early onset of massive hepatic apoptosis leading to death was observed in all nontransgenic mice treated with an anti−Fas antibody. By contrast, hepatic apoptosis was delayed and dramatically reduced in transgenic animals, yielding a 93% survival rate. These results demonstrate that Bcl−2 is able to protect from in vivoFas−mediated cytotoxicity, and could be of significance for preventing fulminant hepatic failure due to viral hepatitis in humans.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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