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Overgrowth of a mouse model of Simpson– Golabi–Behmel syndrome is partly mediated by Indian Hedgehog
Author(s) -
Capurro Mariana I,
Li Fuchuan,
Filmus Jorge
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.98
Subject(s) - hedgehog , indian hedgehog , hedgehog signaling pathway , endocrinology , biology , medicine , null allele , mutant , microbiology and biotechnology , genetics , signal transduction , gene
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.