Overgrowth of a Mouse Model of the Simpson–Golabi–Behmel Syndrome Is Independent of IGF Signaling

The type 1 Simpson–Golabi–Behmel overgrowth syndrome (SGBS1) is caused by loss-of-function mutations of the X-linked GPC3 gene encoding glypican-3, a cell-surface heparan sulfate proteoglycan that apparently plays a negative role in growth control by an unknown mechanism. Mice carrying a Gpc3 gene k...

Full description

Saved in:
Bibliographic Details
Published in:Developmental biology Vol. 243; no. 1; pp. 185 - 206
Main Authors: Chiao, Eric, Fisher, Peter, Crisponi, Laura, Deiana, Manila, Dragatsis, Ioannis, Schlessinger, David, Pilia, Giuseppe, Efstratiadis, Argiris
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.03.2002
Subjects:
Abnormalities, Multiple - genetics
Animals
Disease Models, Animal
Female
Gene Deletion
Gene Expression Regulation
glypican
Glypicans
growth
Heparan Sulfate Proteoglycans - genetics
insulin-like growth factor
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor II - genetics
Male
Mice
Mice, Knockout
proteoglycans
Receptor, IGF Type 1 - genetics
Signal Transduction - genetics
Simpson–Golabi–Behmel syndrome
proteoglycans
growth
insulin-like growth factor
Simpson–Golabi–Behmel syndrome
glypican
ISSN:0012-1606, 1095-564X
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The type 1 Simpson–Golabi–Behmel overgrowth syndrome (SGBS1) is caused by loss-of-function mutations of the X-linked GPC3 gene encoding glypican-3, a cell-surface heparan sulfate proteoglycan that apparently plays a negative role in growth control by an unknown mechanism. Mice carrying a Gpc3 gene knockout exhibited several phenotypic features that resemble clinical hallmarks of SGBS1, including somatic overgrowth, renal dysplasia, accessory spleens, polydactyly, and placentomegaly. In Gpc3/ΔH19 double mutants (lacking GPC3 and also carrying a deletion around the H19 gene region that causes bialellic expression of the closely linked Igf2 gene by imprint relaxation), the Gpc3-null phenotype was exacerbated, while additional SGBS1 features (omphalocele and skeletal defects) were manifested. However, results from a detailed comparative analysis of growth patterns in double mutants lacking GPC3 and also IGF2, IGF1, or the type 1 IGF receptor (IGF1R) provided conclusive genetic evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by sequestering or downregulating an IGF ligand. Nevertheless, our data are compatible with a model positing that there is downstream convergence of the independent signaling pathways in which either IGFs or (indirectly) GPC3 participate.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
ISSN:0012-1606
1095-564X
DOI:10.1006/dbio.2001.0554