| RRC ID |
43900
|
| 著者 |
Hashizume O, Shimizu A, Yokota M, Sugiyama A, Nakada K, Miyoshi H, Itami M, Ohira M, Nagase H, Takenaga K, Hayashi J.
|
| タイトル |
Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis--but not aging--in this model.
|
| 巻・号 |
109(26)
|
| ページ |
10528-33
|
| 公開日 |
2012-6-26
|
| DOI |
10.1073/pnas.1202367109
|
| PII |
1202367109
|
| PMID |
22689997
|
| PMC |
PMC3387115
|
| MeSH |
3T3 Cells
Animals
Base Sequence
Cell Line, Transformed
DNA Primers
DNA, Mitochondrial / genetics*
Diabetes Mellitus, Experimental / genetics*
Lymphoma / genetics*
Mice
Mitochondrial Diseases / genetics*
Mutation*
Phenotype
Polymerase Chain Reaction
Reactive Oxygen Species / metabolism
|
| IF |
9.412
|
| 引用数 |
44
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
