2007 Fiscal Year Final Research Report Summary
Study on IGF-I insensitivity: Function and phenotype of mutated IGF-I receptor gene
| Project/Area Number |
18591153
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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 |
Pediatrics
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| Research Institution | Tottori University |
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Principal Investigator |
KANZAKI Susumu Tottori University, Faculty of Medicine, Professor (90224873)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Ikuo Tottori University, Faculty of Medicine, Associate professor (50252846)
HANAKI Keiichi Tottori University, Faculty of Medicine, Professor (20238041)
NAGAISHI Jun-ichi Tottori University, University Hospital, Asistant professor (90346354)
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| Project Period (FY) |
2006 – 2007
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| Keywords | insulin-like growth factor / IUGR / short stature / Type 1 IGF receptor / IGF insensitivity |
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| Research Abstract |
Context: Insulin-like growth factor (IGF-I) plays key roles in intrauterine fetal growth as well as postnatal growth via IGF-I receptor (IGF-IR). Recently, IGF-IR gene mutations have been reported in four patients with short stature born intrauterine growth retardation (IUGR).
Subjects and Methods: We analyzed the nucleotide sequences of IGF-IR gene in 29 patients with IUGR short stature. Mutated IGF-IR gene was transfected in 3T3-like mouse embryo cells with a targeted disruption of the IGF-IR genes (R-cells). Functions of mutated IGF-IR in transfected R-cells were evaluated by IGF-I binding, IGF-I stimulated DNA synthesis and ss-subunit autophosphorylation and internalization analysis.
Results: 1) A new heterozygous missense mutation at L2 domain of IGF-IR (R431L) was identified in a 6-year-old Japanese girl with IUGR short stature and her mother. 2) DNA synthesis induced by IGF-I was significantly decreased in R-cells transfected with mutated IGF-IR. 3) IRS-2 phosphorylation in response to IGF-I was decreased in R-cells transfected with mutated IGF-IR. 4) Internalization was decreased in R-cells transfected with mutated IGF-IR.
Conclusion: A missense mutation (R431L) causes decreased IGF action by decreased internalization of IGF-IR, and results in growth retardation. The results of this study provide new important information on IUGR short stature with IGF-IR mutation and a role of L2 domain of IGF-IR.
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[Presentation] 小児内分泌の進歩2008
Author(s)
神崎 晋
Organizer
第18回臨床内分泌Update
Place of Presentation
高知市文化プラザかるぽーと
Year and Date
2008-03-15
Description
「研究成果報告書概要(和文)」より
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