Generation and characterization of endonuclease G null mice.
Endonuclease G (endo G) is one of the most abundant nucleases in eukaryotic cells. It is encoded in the nucleus and imported to the mitochondrial intermembrane space. This nuclease is active on single- and double-stranded DNA. We genetically disrupted the endo G gene in mice without disturbing a conserved, overlapping gene of unknown function that is oriented tail to tail with the endo G gene. In these mice, the production of endo G protein is not detected, and the disruption abolishes the nuclease activity of endo G. The absence of endo G has no effect on mitochondrial DNA copy number, structure, or mutation rate over the first five generations. There is also no obvious effect on nuclear DNA degradation in standard apoptosis assays. The endo G null mice are viable and show no age-related or generational abnormalities anatomically or histologically. We infer that this highly conserved protein has no mitochondrial or apoptosis function that can discerned by the assays described here and that it may have a function yet to be determined. The early embryonic lethality of endo G null mice recently reported by others may be due to the disruption of the gene that overlaps the endo G gene.
Irvine
Ryan A
RA
Norris Comprehensive Cancer Center, Rm. 5428, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave., MC9176, Los Angeles, CA 90033, USA. lieber@usc.edu
Adachi
Noritaka
N
Shibata
Darryl K
DK
Cassell
Geoffrey D
GD
Yu
Kefei
K
Karanjawala
Zarir E
ZE
Hsieh
Chih-Lin
CL
Lieber
Michael R
MR
D000818:Animals; D017209:Apoptosis; D015139:Blotting, Southern; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D019076:Transgenes
D002843:Chromatin; D004272:DNA, Mitochondrial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004247:DNA; D004706:Endodeoxyribonucleases; C052391:endonuclease G