Overgrowth of a mouse model of the Simpson-Golabi-Behmel syndrome is independent of IGF signaling

Dev Biol. 2002 Mar 1;243(1):185-206. doi: 10.1006/dbio.2001.0554.


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/DeltaH19 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Deletion
  • Gene Expression Regulation
  • Glypicans
  • Heparan Sulfate Proteoglycans / genetics*
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor II / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • Receptor, IGF Type 1 / genetics*
  • Signal Transduction / genetics


  • Glypicans
  • Heparan Sulfate Proteoglycans
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1

Associated data

  • OMIM/300209
  • OMIM/312870