Functional analysis of endoplasmic reticulum stress-induced genes, NDRG1 and HERPUD1
| Project/Area Number |
15570107
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | NATIONAL CARDIO VA SCULAR CENTER, RESEARCH INSTITUTE |
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Principal Investigator |
MIYATA Toshiyuki NATIONAL CARDIO VA SCULAR CENTER, RESEARCH INSTITUTE, Etiology and Pathogenesis, Director, 病因部, 部長 (90183970)
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| Co-Investigator(Kenkyū-buntansha) |
KOKAME Koichi NATIONAL CARDIO VA SCULAR CENTER, RESEARCH INSTITUTE, Vascular Physiology, Laboratory chief, 脈管生理部, 室長 (40270730)
OKUDA Tomohiko NATIONAL CARDIO VA SCULAR CENTER, RESEARCH INSTITUTE, Etiology and Pathogenesis, Laboratory member, 病因部, 室員 (90360817)
BANNO Fumiaki NATIONAL CARDIO VA SCULAR CENTER, RESEARCH INSTITUTE, Vascular Physiology, Laboratory member, 脈管生理部, 室員 (00373514)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | peripheral neuropathy / Ndrg1 / demyelination / Herp / homocysteine / endoplasmic reticulum stress / Charcot-Marie-Tooth disease / diabetes / 脳虚血 / 耐糖脳 / ノックアウトマウス / 心血管系疾患 / ニューロパチー / ミエリン |
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| Research Abstract |
Ndrg1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Mairie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy. In this study, we generated mice lacking Ndrg1 to analyze its function. Histrogical analysis showed that the sciatic nerve of Ndrg1-defident mice degenerated with demyelination at about 5 weeks of age. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves.
Herp has been isolated as a gene upregulated by atherogenic substance, homocysteine. To investigate the Herp function, we analyzed the phenotypes of Herp-null mice. The blood glucose levels were measured before and after intraperitoneal injection of glucose in Herp-null and wild-type mice. Focal cerebral ischemia was induced in these mice, and developments of cerebral infarction were compared. Herp-null mice were born normally, and exhibited no significant abnormalities. Although their fasting blood glucose levels were normal, the recovery speed after glucose load was moderately impaired. Since the response to insulin was normal, Herp may affect insulin production of pancreatic cells. The volumes of cerebral infarction in Herp-null mice were significantly larger than those in wild-type mice, indicating that Herp protects the brain under ischemia. Herp seems nonessential in normal conditions, but may play a protective role under some critical conditions.
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Report
(3 results)
Research Products
(11 results)
