| First Author | Capurro MI | Year | 2009 |
| Journal | EMBO Rep | Volume | 10 |
| Issue | 8 | Pages | 901-7 |
| PubMed ID | 19590577 | Mgi Jnum | J:157333 |
| Mgi Id | MGI:4430672 | Doi | 10.1038/embor.2009.98 |
| Citation | Capurro MI, et al. (2009) Overgrowth of a mouse model of Simpson-Golabi-Behmel syndrome is partly mediated by Indian hedgehog. EMBO Rep 10(8):901-7 |
| abstractText | Loss-of-function mutations of Glypican 3 (Gpc3) cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS), and developmental overgrowth is observed in Gpc3-null mice, a mouse model for SGBS. We recently reported that GPC3 inhibits Hedgehog (Hh) signalling by inducing its endocytosis and degradation. Here, we show that the developmental overgrowth observed in Gpc3-null mice is, at least in part, a consequence of the hyperactivation of the Hh pathway. We bred Gpc3-null mice with mice that are Hh signalling-deficient owing to the lack of Indian Hh (Ihh), one of the three mammalian Hhs. We found that the Gpc3-null mice showed a 29.9% overgrowth in an Ihh wild-type background, whereas an Ihh-null background partly rescues the overgrowth caused by the lack of Gpc3 as the double mutants were 19.8% bigger than the Ihh-null mice. Consistent with the role of GPC3 in Hh endocytosis and degradation, the Gpc3-null mice show increased levels of Ihh protein and signalling, but similar levels of Ihh messenger RNA. |
