{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:03:11Z","timestamp":1791356591076,"version":"4.3.1"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,7,12]]},"abstract":"<jats:p>Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl\u2013phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role.<\/jats:p>\n               <jats:p>Here, we report that GPC3-deficient mice exhibit several of the clinical features observed in SGBS patients, including developmental overgrowth, perinatal death, cystic and dyplastic kidneys, and abnormal lung development. A proportion of the mutant mice also display mandibular hypoplasia and an imperforate vagina. In the particular case of the kidney, we demonstrate that there is an early and persistent developmental abnormality of the ureteric bud\/collecting system due to increased proliferation of cells in this tissue element.<\/jats:p>\n               <jats:p>The degree of developmental overgrowth of the GPC3-deficient mice is similar to that of mice deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3 knockouts are similar to those of the normal littermates.<\/jats:p>","DOI":"10.1083\/jcb.146.1.255","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"255-264","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":158,"title":["Glypican-3\u2013Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome"],"prefix":"10.1083","volume":"146","author":[{"given":"Danielle F.","family":"Cano-Gauci","sequence":"first","affiliation":[{"name":"aThe Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada"},{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard H.","family":"Song","sequence":"additional","affiliation":[{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"},{"name":"cSunnybrook Health Science Centre, Toronto, Ontario, M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Yang","sequence":"additional","affiliation":[{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"},{"name":"cSunnybrook Health Science Centre, Toronto, Ontario, M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"McKerlie","sequence":"additional","affiliation":[{"name":"cSunnybrook Health Science Centre, Toronto, Ontario, M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Choo","sequence":"additional","affiliation":[{"name":"aThe Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada"},{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Shi","sequence":"additional","affiliation":[{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"},{"name":"cSunnybrook Health Science Centre, Toronto, Ontario, M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Pullano","sequence":"additional","affiliation":[{"name":"aThe Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada"},{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tino D.","family":"Piscione","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu","family":"Grisaru","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Soon","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Sedlackova","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Keith","family":"Tanswell","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"aThe Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada"},{"name":"eThe Amgen Institute, Toronto, Ontario, M5G 2C1 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Yeger","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina A.","family":"Lockwood","sequence":"additional","affiliation":[{"name":"aThe Ontario Cancer Institute, Toronto, Ontario, M5G 2M9 Canada"},{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman D.","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"dHospital for Sick Children, Toronto, Ontario, M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Filmus","sequence":"additional","affiliation":[{"name":"bDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada"},{"name":"cSunnybrook Health Science Centre, Toronto, Ontario, M4N 3M5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,7,12]]},"reference":[{"key":"2023072900420402300_Behmeletal1984","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00291401","article-title":"A new X-linked dysplasia gigantism syndromeidentical with the Simpson dysplasia syndrome?","volume":"67","author":"Behmel","year":"1984","journal-title":"Hum. Genet."},{"key":"2023072900420402300_Bonneh-Barkayetal1997","doi-asserted-by":"crossref","first-page":"12415","DOI":"10.1074\/jbc.272.19.12415","article-title":"Identification of glypican as a dual modulator of the biological activity of fibroblast growth factors","volume":"272","author":"Bonneh-Barkay","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023072900420402300_Brownetal1996","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1093\/hmg\/5.12.2027","article-title":"Imprinting mutation in the Beckwith-Wiedemann syndrome leads to biallelic IGF2 expression through an H19-independent pathway","volume":"5","author":"Brown","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"2023072900420402300_Bullocketal1998","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1101\/gad.12.12.1894","article-title":"Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase","volume":"12","author":"Bullock","year":"1998","journal-title":"Genes Dev."},{"key":"2023072900420402300_Cunliffe-BeamerandFeldman1976","first-page":"895","article-title":"Vaginal septa in miceincidence, inheritance, and effect on reproductive performance","volume":"26","author":"Cunliffe-Beamer","year":"1976","journal-title":"Lab. Anim. Sci."},{"key":"2023072900420402300_David1993","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1096\/fasebj.7.11.8370471","article-title":"Integral membrane heparan sulfate proteoglycans","volume":"7","author":"David","year":"1993","journal-title":"FASEB J."},{"key":"2023072900420402300_N0x29e83e0N0x3769ac0","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1083\/jcb.141.6.1407","article-title":"OCI-5\/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner","volume":"141","author":"Due\u00f1as Gonzalez","year":"1998","journal-title":"J. Cell Biol."},{"key":"2023072900420402300_Eggenschwileretal1997","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1101\/gad.11.23.3128","article-title":"Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes","volume":"11","author":"Eggenschwiler","year":"1997","journal-title":"Genes Dev."},{"key":"2023072900420402300_Filmusetal1995","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1042\/bj3110561","article-title":"Identification of a new membrane-bound heparan sulfate proteoglycan","volume":"311","author":"Filmus","year":"1995","journal-title":"Biochem. J."},{"key":"2023072900420402300_GargantaandBodurtha1992","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ajmg.1320440202","article-title":"Report of another family with Simpson-Golabi-Behmel syndrome and a review of the literature","volume":"44","author":"Garganta","year":"1992","journal-title":"Am. J. Med. Genet."},{"key":"2023072900420402300_Hastie1997","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/39732","article-title":"Disomy and disease resolved?","volume":"389","author":"Hastie","year":"1997","journal-title":"Nature."},{"key":"2023072900420402300_Hatadaetal1996","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng1096-171","article-title":"An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann Syndrome","volume":"14","author":"Hatada","year":"1996","journal-title":"Nat. Genet."},{"key":"2023072900420402300_Hughes-Benzieetal1996","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/(SICI)1096-8628(19961211)66:2<227::AID-AJMG20>3.0.CO;2-U","article-title":"Simpson-Golabi-Behmel Syndromegenotype\/phenotype analysis of 18 affected males from 7 unrelated families","volume":"66","author":"Hughes-Benzie","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"2023072900420402300_Jacksonetal1997","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1242\/dev.124.20.4113","article-title":"dally, a Drosophila glypican, controls cellular responses to the TGF-beta-related morphogen Dpp","volume":"124","author":"Jackson","year":"1997","journal-title":"Development."},{"key":"2023072900420402300_Jacobsonetal1997","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0092-8674(00)81873-5","article-title":"Programmed cell death in animal development","volume":"88","author":"Jacobson","year":"1997","journal-title":"Cell."},{"key":"2023072900420402300_Kleefetal1998","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1172\/JCI4105","article-title":"The cell surface heparan sulfate proteoglycan glypican-1 regulates growth factor in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer","volume":"102","author":"Kleef","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072900420402300_Lauetal1994","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1101\/gad.8.24.2953","article-title":"Loss of the imprinted IGF2\/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality","volume":"8","author":"Lau","year":"1994","journal-title":"Genes Dev."},{"key":"2023072900420402300_Leeetal1999","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.1073\/pnas.96.9.5203","article-title":"Loss of imprinting of a paternally expressed transcript, with antisense orientation to KvLqt1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting","volume":"96","author":"Lee","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072900420402300_Leightonetal1995","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/375034a0","article-title":"Disruption of imprinting caused by deletion of the H19 gene region in mice","volume":"375","author":"Leighton","year":"1995","journal-title":"Nature."},{"key":"2023072900420402300_Lindsayetal1997","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1136\/jmg.34.6.480","article-title":"Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome","volume":"34","author":"Lindsay","year":"1997","journal-title":"J. Med. Genet."},{"key":"2023072900420402300_Ludwigetal1996","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1006\/dbio.1996.0182","article-title":"Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds","volume":"177","author":"Ludwig","year":"1996","journal-title":"Dev. Biol."},{"key":"2023072900420402300_Nakatoetal1995","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1242\/dev.121.11.3687","article-title":"The division abnormally delayed (dally) genea putative integral membrane proteoglycan required for cell division patterning during postembryonic development of the nervous system in Drosophila","volume":"121","author":"Nakato","year":"1995","journal-title":"Development."},{"key":"2023072900420402300_Nerietal1988","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/ajmg.1320300130","article-title":"Simpson-Golabi-Behmel syndromean X-linked encephalo-tropho-schisis syndrome","volume":"30","author":"Neri","year":"1988","journal-title":"Am. J. Med. Genet."},{"key":"2023072900420402300_Nerietal1998","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/(SICI)1096-8628(19981002)79:4<279::AID-AJMG9>3.0.CO;2-H","article-title":"Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome","volume":"79","author":"Neri","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"2023072900420402300_Orstaviketal1995","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/ajmg.1320560219","article-title":"Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome","volume":"56","author":"Orstavik","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"2023072900420402300_Pellegrinietal1998","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/(SICI)1097-0177(199812)213:4<431::AID-AJA8>3.0.CO;2-7","article-title":"Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome","volume":"213","author":"Pellegrini","year":"1998","journal-title":"Dev. Dyn."},{"key":"2023072900420402300_Piliaetal1996","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/ng0396-241","article-title":"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome","volume":"12","author":"Pilia","year":"1996","journal-title":"Nat. Genet."},{"key":"2023072900420402300_Saundersetal1997","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1006\/dbio.1997.8690","article-title":"Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain","volume":"190","author":"Saunders","year":"1997","journal-title":"Dev. Biol."},{"key":"2023072900420402300_Songetal1997","doi-asserted-by":"crossref","first-page":"7574","DOI":"10.1074\/jbc.272.12.7574","article-title":"OCI-5\/rat glypican-3 binds to fibroblast growth factor-2 but not to insulin-like growth factor-2","volume":"272","author":"Song","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023072900420402300_SorokinandEkblom1992","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/ki.1992.101","article-title":"Development of tubular and glomerular cells of the kidney","volume":"41","author":"Sorokin","year":"1992","journal-title":"Kidney Int."},{"key":"2023072900420402300_Steinfeldetal1996","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1083\/jcb.133.2.405","article-title":"Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican","volume":"133","author":"Steinfeld","year":"1996","journal-title":"J. Cell Biol."},{"key":"2023072900420402300_Stippetal1994","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1083\/jcb.124.1.149","article-title":"Cerebroglycanan integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation","volume":"124","author":"Stipp","year":"1994","journal-title":"J. Cell Biol."},{"key":"2023072900420402300_Sunetal1997","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/39797","article-title":"Transactivation of Igf2 in a mouse model of Beckwith-Wiedemann syndrome","volume":"389","author":"Sun","year":"1997","journal-title":"Nature."},{"key":"2023072900420402300_VainioandMuller1997","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/S0092-8674(00)80363-3","article-title":"Inductive tissue interactions, cell signaling, and the control of kidney organogenesis","volume":"90","author":"Vainio","year":"1997","journal-title":"Cell."},{"key":"2023072900420402300_Veugelersetal1997","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1006\/geno.1996.4518","article-title":"Characterization of glypican-5 and chromosomal localization of human GPC5, a new member of the glypican gene family","volume":"40","author":"Veugelers","year":"1997","journal-title":"Genomics."},{"key":"2023072900420402300_Wangetal1994","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/372464a0","article-title":"Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2\/Mpr gene","volume":"372","author":"Wang","year":"1994","journal-title":"Nature."},{"key":"2023072900420402300_Watanabeetal1995","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1083\/jcb.130.5.1207","article-title":"K-glypicana novel GPI-linked heparan sulfate proteoglycan that is highly expressed in developing brain and kidney","volume":"130","author":"Watanabe","year":"1995","journal-title":"J. Cell Biol."},{"key":"2023072900420402300_WeksbergandSquire1996","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/(SICI)1096-911X(199611)27:5<462::AID-MPO13>3.0.CO;2-C","article-title":"Molecular biology of Beckwith-Wiedemann syndrome","volume":"27","author":"Weksberg","year":"1996","journal-title":"Med. Pediatr. Oncol."},{"key":"2023072900420402300_Weksbergetal1996","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ng0396-225","article-title":"Glypicansa growing trend","volume":"12","author":"Weksberg","year":"1996","journal-title":"Nat. Genet."},{"key":"2023072900420402300_Wengetal1995","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1177\/000992289503400605","article-title":"Beckwith-Wiedemann syndrome","volume":"34","author":"Weng","year":"1995","journal-title":"Clin. Pediatr."},{"key":"2023072900420402300_WoolfandCale1997","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/00041552-199701000-00003","article-title":"Roles of growth factors in renal development","volume":"6","author":"Woolf","year":"1997","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"2023072900420402300_Yanetal1997","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1101\/gad.11.8.973","article-title":"Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development","volume":"11","author":"Yan","year":"1997","journal-title":"Genes Dev."},{"key":"2023072900420402300_Zhangetal1997","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/387151a0","article-title":"Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome","volume":"387","author":"Zhang","year":"1997","journal-title":"Nature."}],"container-title":["The Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/146\/1\/255\/1850717\/9904071.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/146\/1\/255\/1850717\/9904071.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T00:43:03Z","timestamp":1690591383000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/146\/1\/255\/29480\/Glypican-3-Deficient-Mice-Exhibit-Developmental"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7,12]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,7,12]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.146.1.255","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,7,12]]}}}