Developmental retinal apoptosis in Ku86-/- mice.
The nonhomologous DNA end-joining pathway (NHEJ), a major pathway for repairing DNA double-strand breaks (DSBs), is essential for maintaining genomic stability. Knockout animals for components in this pathway demonstrate a distinct pattern of cell death in the developing brain. Here we demonstrate that cell death is also present in the developing retina of E14.5 Ku86-deficient mouse embryos, suggesting that the increase in cell death in the retina is associated with chromosome breaks. In the adult retina, we do not find continuing apoptosis, but interestingly, we find decreased numbers of total neuronal cells. This suggests that the increased retinal apoptosis during embryogenesis causes the reduction in cell numbers observed in the adult retina. This analysis of the retina provides the first opportunity to formally test the hypothesis that embryonic apoptosis accounts for reduced total cell numbers in adult Ku86-/- mice.
Karanjawala
Zarir E
ZE
Norris Comprehensive Cancer Center, Room 5428, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9176, USA.
Hinton
David R
DR
Oh
Euikyun
E
Hsieh
Chih Lin
CL
Lieber
Michael R
MR
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D019457:Chromosome Breakage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000254:growth & development
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000606512:Xrcc5 protein, mouse; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen