Deletions are easy detectable in cochlear mitochondrial DNA of Cu/Zn superoxide dismutase gene knockout mice.
OBJECTIVE
To investigate the tissue specificity of reactive oxygen species (ROS) damage to mitochondrial DNA (mtDNA) and to determine whether cochlear mtDNA is a sensitive target for ROS damage.


METHODS
10 Cu/ZnSOD gene (Cu/Zn superoxide dismutase gene, Sod1) knockout mice and 16 wild-type mice were analyzed by nested polymerase chain reaction (PCR).


RESULTS
Three deletions were detected in various tissues of Sod1 knockout mice. MtDNA3867bp and mtDNA3726bp deletions were the most visible, and mtDNA4236bp deletion was barely detected in these tissues. There were obvious differences in the ratio of deleted mtDNA/total mtDNA in different tissue. Deleted mtDNA was most abundant in the liver and kidney and less in cochlea, heart and brain. The lowest was in spleen and skin. The ratio in various tissues was 3 - 20 times in Sod1 knockout mice over wild-type mice. In cochlea, the ratio was about 15.


CONCLUSIONS
Without the protection of Sod1, ROS can lead to mtDNA deletions in various tissues with significant tissue specificity. Cochlear mtDNA is a sensitive target for ROS damage.
Zhang
Xinxin
X
PLA General Hospital, Deptartment of Otolaryngology, Beijing 100853, China.
Han
Dongyi
D
Ding
Dalian
D
Dai
Pu
P
Yang
Weiyan
W
Jiang
Sichang
S
Salvi
Richard J
RJ
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics; D017384:Sequence Deletion; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*
D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D013482:Superoxide Dismutase