Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development.
The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx's physiologic function remains unknown. To elucidate the in vivo role of Daxx, we have generated Daxx-deficient mice. Surprisingly, rather than a hyperproliferative disorder expected from the loss of a pro-apoptotic gene, mutation of Daxx results in extensive apoptosis and embryonic lethality. These findings argue against a role for Daxx in promoting Fas-induced cell death and suggest that Daxx either directly or indirectly suppresses apoptosis in the early embryo.
Michaelson
J S
JS
Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bader
D
D
Kuo
F
F
Kozak
C
C
Leder
P
P
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002875:Chromosomes / Q000235:genetics; D003001:Cloning, Molecular; D056970:Co-Repressor Proteins; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020043:Genes, Essential / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D019853:O(6)-Methylguanine-DNA Methyltransferase