Endonuclease G is required for early embryogenesis and normal apoptosis in mice.
Endonuclease G (EndoG) is a nuclear-encoded mitochondrial protein reported to be important for both nuclear DNA fragmentation during apoptosis and mitochondrial DNA replication. To evaluate the in vivo function of EndoG, we have investigated the effects of EndoG deficiency in cells and mice. We found that EndoG homozygous mutant embryos die between embryonic days 2.5 and 3.5. Mitochondrial DNA copy numbers in ovulated oocytes from EndoG heterozygous mutant and wild-type mice are similar, suggesting that EndoG is involved in a cellular function unrelated to mitochondrial DNA replication. Interestingly, we found that cells from EndoG heterozygous mutant mice exhibit increased resistance to both tumor necrosis factor alpha- and staurosporine-induced cell death. Moreover, spontaneous cell death of spermatogonia in EndoG heterozygous mutant mice is significantly reduced compared with wild-type mice. DNA fragmentation is also reduced in EndoG+/- thymocytes and splenocytes compared with wild-type cells, as well as in EndoG+/- thymus in vivo compared with that of the wild-type mice, on activation of apoptosis. These findings indicate that EndoG is essential during early embryogenesis and plays a critical role in normal apoptosis and nuclear DNA fragmentation.
Zhang
Jianhua
J
Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. jianhua.zhang@uc.edu
Dong
Mei
M
Li
Lily
L
Fan
Yunxia
Y
Pathre
Purnima
P
Dong
Jin
J
Lou
Danwen
D
Wells
James M
JM
Olivares-Villagómez
Danyvid
D
Van Kaer
Luc
L
Wang
Xiaodong
X
Xu
Ming
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011994:Recombinant Proteins / Q000378:metabolism; D013093:Spermatogonia / Q000473:pathology; D013737:Testis / Q000196:embryology / Q000201:enzymology; D014162:Transfection
D017931:DNA Primers; D004272:DNA, Mitochondrial; D011994:Recombinant Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G