Mice Lacking Dad1, the Defender against Apoptotic Death-1, Express Abnormal N-Linked Glycoproteins and Undergo Increased Embryonic Apoptosis

[摘要] Dad1hasbeenshowntoplayaroleinpreventingapoptoticcelldeathandinregulatinglevelsofN-linkedglycosylationinSaccharomycescerevisiaeandtheBHKhamstercellline.ToaddresstheinvivoroleofDad1intheseprocessesduringmulticellulardevelopment,wehaveanalyzedmicecarryinganullalleleforDad1.EmbryoshomozygousforthismutationexpressabnormalN-glycosylatedproteinsandaredevelopmentallydelayedbyembryonicday7.5.Suchmutantsexhibitaberrantmorphology,impairedmesodermaldevelopment,andincreasedlevelsofapoptosisinspecifictissues.Thesedefectsculminateinhomozygousembryosfailingtoturntheposterioraxisandsubsequentlethalitybyembryonicday10.5.Thus,Dad1isrequiredforproperprocessingofN-linkedglycoproteinsandforcertaincellsurvivalinthemouse.