| Project/Area Number |
13680702
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
|---|
Principal Investigator |
MIYATA Toshiuyuki NATIONAL CARDIOVAS CULARCENTER, RESEARCH INSTITUTE, Director, 病因部, 部長 (90183970)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOKAME Koichi NATIONAL CARDIOVASCULAR CENTER, RESEARCH INSITUTE, Laboratory chief, 脈管生理部, 室長 (40270730)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Homocysteine / hereditary motor and sensory neuropathy / NDRG1 / mouse model / demyelination / sensory impairment / ノックアウトマウス / 運動感覚障害 / ニューロパチー / シュワン細胞 / 運動障害 / マウスモデル / 脱ミエリン化 / 神経軸索 / 遺伝子欠失動物 / 神経障害遺伝子 / loxP |
|---|
| Research Abstract |
We previously identified NDRG1 as a homocysteine responsive gene. It encodes 394 amino acids with three repeats of ten amino acids at the C-terminal end. Recently, NDRG1 has been identified as a responsible gene for hereditary motor and sensory neuropathy-Lom (HMSNL). HMSNL shows features of Schwann cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axon-glia interactions play a major role in its pathogenesis. We successfully generated mice lacking for NDRG1 gene. The promoter and exon 1 region of NDRG1 gene was completely deleted in this mouse. We could detect no NDRG1 protein in its kidney, where NDRG1 is abundantly expressed. The homozygous mutant mice were fertile, but exhibited growth retardation. The NDRG1-deficient mice showed extreme dysfunction in motor activity compared with wild-type mice. Thus, the Ndrg1-deficient mice should be good model animals for physiological analyses of human peripheral neurodegenerative diseases, and useful for analysis of interaction between Schwann cells and neurons.
|
