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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 230217.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Mono-allelic expression of the IGF-I receptor does not affect IGF responses in human fibroblasts
Authors:Hammer, E.; Kutsche, K.; Haag, F.; Ullrich, K.; Sudbrak, R.; Willig, R. P.; Braulke, T.; Kubler, B.
Date of Publication (YYYY-MM-DD):2004-10
Title of Journal:European Journal of Endocrinology
Journal Abbrev.:Eur J Endocrinol
Issue / Number:4
Start Page:521
End Page:529
Copyright:© 2004 by European Federation of Endocrine Societies
Review Status:not specified
Audience:Experts Only
Abstract / Description:OBJECTIVE: It has been suggested that mono-allelic deletion of the IGF-I receptor gene is causally related to severe intrauterine and postnatal growth deficiency whereas no IGF-I resistance was observed in the patients' fibroblasts. The expression and regulation of the growth-modulating IGF binding proteins (IGFBPs) have been investigated in serum and fibroblasts of a short girl with mono-allelic loss of the distal long arm of chromosome 15 (15q26.1-qter).
PATIENT AND METHODS: The mono-allelic loss of the IGF-I receptor (IGF1R) gene was confirmed in a child with prenatal and severe postnatal growth retardation by fluorescence in situ hybridization, and was evaluated on the protein level in fibroblasts of the patient by FACS analysis and IGF cross-linkage. Additionally, expression of IGFBPs and cell-mediated degradation of IGFBP-3 were examined in the patient's fibroblasts.
RESULTS: Levels of GH, IGF-I, and IGFBP-3 were above the 95th percentile in the serum of the 3-year-old girl with a mono-allelic deletion of the IGF1R gene, suggesting IGF-I resistance. In the patient's fibroblasts the IGF-I receptor concentration was half that in control cells. Whereas the pattern of secreted IGFBPs in response to IGFs was not altered, the abundance of secreted IGFBPs was higher in the patient's cells than in controls. Moreover, fibroblast-mediated degradation of 125I-labeled IGFBP-3 appears to be reduced in the patient's fibroblasts. The higher abundance of IGFBPs in the patient's fibroblasts might be responsible for the lack of IGF-I-stimulated [alpha-1-14C]methylaminoisobutyric acid transport.
CONCLUSION: Our results suggest that the expression and regulation of IGFBPs in tissues from patients with mono-allelic deletion of the IGF-I receptor gene may lead to IGF sequestration and contribute to IGF-I resistance and growth retardation.
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Children's Hospital, University of Hamburg 20246 Hamburg, Germany
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