| Project/Area Number |
22590925
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Niigata University |
|---|
Principal Investigator |
SATO Toshiya 新潟大学, 脳研究所, 助教 (90359703)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
OSAMU Onodera 新潟大学, 脳研究所, 教授 (20303167)
|
|---|
| Research Collaborator |
SACHIKO Hirokawa 新潟大学, 脳研究所, 技術職員
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 脳神経疾患 / ALS / TDP-43 / 疾患モデル / 筋萎縮性側索硬化症 / 初期胚発生 |
|---|
| Research Abstract |
To investigate the physiological functions of TAR DNA-binding protein 43 kDa (TDP-43), we established TDP-43 conditional knockout (cKO) mice and evaluated the validity of disease models for amyotrophic lateral sclerosis (ALS). As a result of the autoregulation, TDP-43 mRNAs were recovered to wild type levels in various tissues of heterozygous TDP-43 KO (Tardbp^+/-) mice. This recovery would prevent from the emergence of abnormal phenotypes. On the other hand, TDP-43 mRNA level in unfertilized oocytes obtained from heterozygous mice was reduced by half. This haploinsufficiency would account for the delay of early embryonic development. Because homozygous (Tardbp^-/-) mice died by early post-implantation stage, we established neuron-specific KO (Tardbp^flox/flox、NSE-Cre^+) mice using NSE39-Cre mice. Neuron-specific KO mice showed sever neurological phenotypes with a median survival of 20 days. Pathologically, chromatolysis and abnormal-shaped mitochondria, characteristic features of ALS, were observed in lumbar motor neurons.
|
