| Project/Area Number |
24591512
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OKADA Shin-ichi 鳥取大学, 医学部, 准教授 (50343281)
MURAKAMI Jun 鳥取大学, 医学部附属病院, 講師 (90362889)
HANAKI Keiichi 鳥取大学, 医学部, 教授 (20238041)
SONOYAMA Yuki (KAWASHIMA Yuki) 鳥取大学, 医学部, 講師 (20403412)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | IGF-I受容体異常症 / 成長ホルモン不応症 / SGA性低身長 / IGF-I / 小胞体関連分解 / Castleman病 / IL-6 / 偽性副甲状腺機能低下症 / 遺伝子変異 |
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| Outline of Final Research Achievements |
We identified two novel heterozygous nonsense mutations of type 1 IGF receptor (IGF-IR) gene in 9-year-old boy (p.Q1220X) and 3-year-old girl (p.W1219X) with SGA short stature. The cells transfected with these mutated IGF-1R genes showed an extremely low level of the IGF-1R protein compared to those with wild type. These mutations cause premature stop codon (PTC) in exon 21, and result in the absence of the carboxyl terminal fragment of IGF-1R. Quality of protein production is usually controlled by two mechanism; nonsense-mediated mRNA decay (NMD) in mRNA stage and endoplasmic reticulum associated degradation (ERAD) in protein production. Emetine, that blocks NMD, did not improve IGF-IR mRNA expression in transfected cells. Whereas, addition of MG132, that blocks ERAD, could rescue the reduced IGF-IR protein productio. From the above results, we speculated that the mutation (p.W1219X and p.Q1220X) lead to decrease IGF-1R protein expression through ERAD, result in growth failure.
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