{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:39:59Z","timestamp":1791153599235,"version":"4.1.0"},"reference-count":63,"publisher":"The Company of Biologists","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,15]]},"abstract":"<jats:p>Hereditary multiple exostoses (HME) is a genetically heterogeneous human disease characterized by the development of bony outgrowths near the ends of long bones. HME results from mutations in EXT1 and EXT2,genes that encode glycosyltransferases that synthesize heparan sulfate chains. To study the relationship of the disease to mutations in these genes, we generated Ext2-null mice by gene targeting. Homozygous mutant embryos developed normally until embryonic day 6.0, when they became growth arrested and failed to gastrulate, pointing to the early essential role for heparan sulfate in developing embryos. Heterozygotes had a normal lifespan and were fertile; however, analysis of their skeletons showed that about one-third of the animals formed one or more ectopic bone growths (exostoses). Significantly, all of the mice showed multiple abnormalities in cartilage differentiation, including disorganization of chondrocytes in long bones and premature hypertrophy in costochondral cartilage. These changes were not attributable to a defect in hedgehog signaling, suggesting that they arise from deficiencies in other heparan sulfate-dependent pathways. The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular mechanisms underlying the development of exostoses.<\/jats:p>","DOI":"10.1242\/dev.02088","type":"journal-article","created":{"date-parts":[[2005,10,20]],"date-time":"2005-10-20T13:46:39Z","timestamp":1129815999000},"page":"5055-5068","source":"Crossref","is-referenced-by-count":222,"title":["Mice deficient in Ext2 lack heparan sulfate and develop exostoses"],"prefix":"10.1242","volume":"132","author":[{"given":"Dominique","family":"Stickens","sequence":"first","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143-0452,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly M.","family":"Zak","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0687,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Rougier","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143-0452,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Esko","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0687,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zena","family":"Werb","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143-0452,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605191222400_REF1","doi-asserted-by":"crossref","unstructured":"Ahn, J., Ludecke, H. J., Lindow, S., Horton, W. A., Lee, B.,Wagner, M. J., Horsthemke, B. and Wells, D. E. (1995). Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nat. Genet.11,137-143.","DOI":"10.1038\/ng1095-137"},{"key":"2021042605191222400_REF2","unstructured":"Albrecht, U., Eichele, G., Helms, J. A. and Lu, H.(1997). Visualization of gene expression patterns by in situ hybridization. In Molecular and Cellular Methods in Developmental Toxicology (ed. G. Daston), pp. 23-48. Boca Raton: CRC Press."},{"key":"2021042605191222400_REF3","doi-asserted-by":"crossref","unstructured":"Ang, S. L., Conlon, R. A., Jin, O. and Rossant, J.(1994). Positive and negative signals from mesoderm regulate the expression of mouse Otx2 in ectoderm explants. Development120,2979-2989.","DOI":"10.1242\/dev.120.10.2979"},{"key":"2021042605191222400_REF4","doi-asserted-by":"crossref","unstructured":"Arman, E., Haffner-Krausz, R., Chen, Y., Heath, J. K. and Lonai,P. (1998). Targeted disruption of fibroblast growth factor(FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. Proc. Natl. Acad. Sci. USA95,5082-5087.","DOI":"10.1073\/pnas.95.9.5082"},{"key":"2021042605191222400_REF5","doi-asserted-by":"crossref","unstructured":"Bame, K. J. and Esko, J. D. (1989). Undersulfated heparan sulfate in a Chinese hamster ovary cell mutant defective in heparan sulfate N-sulfotransferase. J. Biol. Chem.264,8059-8065.","DOI":"10.1016\/S0021-9258(18)83150-7"},{"key":"2021042605191222400_REF6","doi-asserted-by":"crossref","unstructured":"Barnes, J. D., Crosby, J. L., Jones, C. M., Wright, C. V. and Hogan, B. L. (1994). Embryonic expression of Lim-1, the mouse homolog of Xenopus Xlim-1, suggests a role in lateral mesoderm differentiation and neurogenesis. Dev. Biol.161,168-178.","DOI":"10.1006\/dbio.1994.1018"},{"key":"2021042605191222400_REF7","doi-asserted-by":"crossref","unstructured":"Basheeruddin, K., Stein, P., Strickland, S. and Williams, D. L. (1987). Expression of the murine apolipoprotein E gene is coupled to the differentiated state of F9 embryonal carcinoma cells. Proc. Natl. Acad. Sci. USA84,709-713.","DOI":"10.1073\/pnas.84.3.709"},{"key":"2021042605191222400_REF8","doi-asserted-by":"crossref","unstructured":"Bellaiche, Y., The, I. and Perrimon, N. (1998). Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature394, 85-88.","DOI":"10.1038\/27932"},{"key":"2021042605191222400_REF9","doi-asserted-by":"crossref","unstructured":"Bornemann, D. J., Duncan, J. E., Staatz, W., Selleck, S. and Warrior, R. (2004). Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways. Development131,1927-1938.","DOI":"10.1242\/dev.01061"},{"key":"2021042605191222400_REF10","doi-asserted-by":"crossref","unstructured":"Ciruna, B. and Rossant, J. (2001). FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev. Cell1, 37-49.","DOI":"10.1016\/S1534-5807(01)00017-X"},{"key":"2021042605191222400_REF11","doi-asserted-by":"crossref","unstructured":"Conlon, F. L., Lyons, K. M., Takaesu, N., Barth, K. S., Kispert,A., Herrmann, B. and Robertson, E. J. (1994). A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development120,1919-1928.","DOI":"10.1242\/dev.120.7.1919"},{"key":"2021042605191222400_REF12","unstructured":"Cook, A., Raskind, W., Blanton, S. H., Pauli, R. M., Gregg, R. G., Francomano, C. A., Puffenberger, E., Conrad, E. U., Schmale, G.,Schellenberg, G. et al. (1993). Genetic heterogeneity in families with hereditary multiple exostoses. Am. J. Hum. Genet.53,71-79."},{"key":"2021042605191222400_REF13","doi-asserted-by":"crossref","unstructured":"Crossley, P. H. and Martin, G. R. (1995). The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. Development121,439-451.","DOI":"10.1242\/dev.121.2.439"},{"key":"2021042605191222400_REF14","doi-asserted-by":"crossref","unstructured":"Esko, J. D. and Selleck, S. B. (2002). Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu. Rev. Biochem.71,435-471.","DOI":"10.1146\/annurev.biochem.71.110601.135458"},{"key":"2021042605191222400_REF15","doi-asserted-by":"crossref","unstructured":"Feldman, B., Poueymirou, W., Papaioannou, V. E., DeChiara, T. M. and Goldfarb, M. (1995). Requirement of FGF-4 for postimplantation mouse development. Science267,246-249.","DOI":"10.1126\/science.7809630"},{"key":"2021042605191222400_REF16","unstructured":"Ferguson, C., Alpern, E., Miclau, T. and Helms, J. A.(1999). Does adult fracture repair recapitulate embryonic skeletal formation? Mech. Dev.87, 57-66."},{"key":"2021042605191222400_REF17","doi-asserted-by":"crossref","unstructured":"Garcia-Garcia, M. J. and Anderson, K. V.(2003). Essential role of glycosaminoglycans in Fgf signaling during mouse gastrulation. Cell114,727-737.","DOI":"10.1016\/S0092-8674(03)00715-3"},{"key":"2021042605191222400_REF18","doi-asserted-by":"crossref","unstructured":"Han, C., Belenkaya, T. Y., Khodoun, M., Tauchi, M. and Lin,X. (2004). Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development131,1563-1575.","DOI":"10.1242\/dev.01051"},{"key":"2021042605191222400_REF19","unstructured":"Hecht, J. T., Hogue, D., Strong, L. C., Hansen, M. F., Blanton,S. H. and Wagner, M. (1995). Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. Am. J. Hum. Genet.56,1125-1131."},{"key":"2021042605191222400_REF20","doi-asserted-by":"crossref","unstructured":"Hefti, E., Trechsel, U., Rufenacht, H. and Fleisch, H.(1980). Use of dermestid beetles for cleaning bones. Calcif. Tissue Int.31,45-47.","DOI":"10.1007\/BF02407166"},{"key":"2021042605191222400_REF21","doi-asserted-by":"crossref","unstructured":"Hennekam, R. C. M. (1991). Hereditary multiple exostosis. J. Med. Genet.28,262-266.","DOI":"10.1136\/jmg.28.4.262"},{"key":"2021042605191222400_REF22","doi-asserted-by":"crossref","unstructured":"Hermesz, E., Mackem, S. and Mahon, K. A.(1996). Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo. Development122, 41-52.","DOI":"10.1242\/dev.122.1.41"},{"key":"2021042605191222400_REF23","doi-asserted-by":"crossref","unstructured":"Hilton, M. J., Gutierrez, L., Martinez, D. A. and Wells, D. E. (2005). EXT1 regulates chondrocyte proliferation and differentiation during endochondral bone development. Bone36,379-386.","DOI":"10.1016\/j.bone.2004.09.025"},{"key":"2021042605191222400_REF24","doi-asserted-by":"crossref","unstructured":"Karsenty, G. and Wagner, E. F. (2002). Reaching a genetic and molecular understanding of skeletal development. Dev. Cell2,389-406.","DOI":"10.1016\/S1534-5807(02)00157-0"},{"key":"2021042605191222400_REF25","doi-asserted-by":"crossref","unstructured":"Kelly, O. G., Pinson, K. I. and Skarnes, W. C.(2004). The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development131,2803-2815.","DOI":"10.1242\/dev.01137"},{"key":"2021042605191222400_REF26","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Chung, U. I., Schipani, E., Starbuck, M.,Karsenty, G., Katagiri, T., Goad, D. L., Lanske, B. and Kronenberg, H. M. (2002). PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development129,2977-2986.","DOI":"10.1242\/dev.129.12.2977"},{"key":"2021042605191222400_REF27","doi-asserted-by":"crossref","unstructured":"Koziel, L., Kunath, M., Kelly, O. G. and Vortkamp, A.(2004). Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev. Cell6, 801-813.","DOI":"10.1016\/j.devcel.2004.05.009"},{"key":"2021042605191222400_REF28","doi-asserted-by":"crossref","unstructured":"Le Merrer, M., Legeai-Mallet, L., Jeannin, P. M., Horsthemke,B., Schinzel, A., Plauchu, H., Toutain, A., Achard, F., Munnich, A. and Maroteaux, P. (1994). A gene for hereditary multiple exostoses maps to chromosome 19p. Hum. Mol. Genet.3, 717-722.","DOI":"10.1093\/hmg\/3.5.717"},{"key":"2021042605191222400_REF29","doi-asserted-by":"crossref","unstructured":"Lee, J. S., von der Hardt, S., Rusch, M. A., Stringer, S. E.,Stickney, H. L., Talbot, W. S., Geisler, R., Nusslein-Volhard, C.,Selleck, S. B., Chien, C. B. et al. (2004). Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron44,947-960.","DOI":"10.1016\/j.neuron.2004.11.029"},{"key":"2021042605191222400_REF30","doi-asserted-by":"crossref","unstructured":"Lin, X. (2004). Functions of heparan sulfate proteoglycans in cell signaling during development. Development131,6009-6021.","DOI":"10.1242\/dev.01522"},{"key":"2021042605191222400_REF31","doi-asserted-by":"crossref","unstructured":"Lin, X., Wei, G., Shi, Z., Dryer, L., Esko, J. D., Wells, D. E. and Matzuk, M. M. (2000). Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice. Dev. 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The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nat. Genet.19,158-161.","DOI":"10.1038\/514"},{"key":"2021042605191222400_REF35","doi-asserted-by":"crossref","unstructured":"McCormick, C., Duncan, G., Goutsos, K. T. and Tufaro, F.(2000). The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc. Natl. Acad. Sci. USA97,668-673.","DOI":"10.1073\/pnas.97.2.668"},{"key":"2021042605191222400_REF36","doi-asserted-by":"crossref","unstructured":"McLeod, M. J. (1980). Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology22,299-301.","DOI":"10.1002\/tera.1420220306"},{"key":"2021042605191222400_REF37","doi-asserted-by":"crossref","unstructured":"Minina, E., Wenzel, H. M., Kreschel, C., Karp, S., Gaffield, W.,McMahon, A. P. and Vortkamp, A. (2001). 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(2002). Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim. Biophys. Acta1573,312-318.","DOI":"10.1016\/S0304-4165(02)00398-7"},{"key":"2021042605191222400_REF41","unstructured":"Naski, M. C. and Ornitz, D. M. (1998). FGF signaling in skeletal development. Front. Biosci.3,D781-D794."},{"key":"2021042605191222400_REF42","doi-asserted-by":"crossref","unstructured":"Nieto, M. A., Bennett, M. F., Sargent, M. G. and Wilkinson, D. G. (1992). Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene. Development116,227-237.","DOI":"10.1242\/dev.116.1.227"},{"key":"2021042605191222400_REF43","doi-asserted-by":"crossref","unstructured":"Ornitz, D. M. and Marie, P. J. (2002). FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev.16,1446-1465.","DOI":"10.1101\/gad.990702"},{"key":"2021042605191222400_REF44","doi-asserted-by":"crossref","unstructured":"Poirier, F., Chan, C. T., Timmons, P. M., Robertson, E. J.,Evans, M. J. and Rigby, P. W. (1991). The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development113,1105-1114.","DOI":"10.1242\/dev.113.4.1105"},{"key":"2021042605191222400_REF45","doi-asserted-by":"crossref","unstructured":"Senay, C., Lind, T., Muguruma, K., Tone, Y., Kitagawa, H.,Sugahara, K., Lidholt, K., Lindahl, U. and Kusche-Gullberg, M.(2000). The EXT1\/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis. EMBO Rep.1, 282-286.","DOI":"10.1093\/embo-reports\/kvd045"},{"key":"2021042605191222400_REF46","doi-asserted-by":"crossref","unstructured":"Shawlot, W. and Behringer, R. R. (1995). Requirement for Lim1 in head-organizer function. Nature374,425-430.","DOI":"10.1038\/374425a0"},{"key":"2021042605191222400_REF47","doi-asserted-by":"crossref","unstructured":"Simeone, A., Acampora, D., Mallamaci, A., Stornaiuolo, A.,D'Apice, M. R., Nigro, V. and Boncinelli, E. (1993). A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J.12,2735-2747.","DOI":"10.1002\/j.1460-2075.1993.tb05935.x"},{"key":"2021042605191222400_REF48","doi-asserted-by":"crossref","unstructured":"Smith, D. E., Franco del Amo, F. and Gridley, T.(1992). Isolation of Sna, a mouse gene homologous to the Drosophila genes snail and escargot: its expression pattern suggests multiple roles during postimplantation development. Development116,1033-1039.","DOI":"10.1242\/dev.116.4.1033"},{"key":"2021042605191222400_REF49","doi-asserted-by":"crossref","unstructured":"Soegiarto, D. W., Kiachopoulos, S., Schipani, E., Juppner, H.,Erben, R. G. and Lanske, B. (2001). Partial rescue of PTH\/PTHrP receptor knockout mice by targeted expression of the Jansen transgene. Endocrinology142,5303-5310.","DOI":"10.1210\/endo.142.12.8553"},{"key":"2021042605191222400_REF50","doi-asserted-by":"crossref","unstructured":"Solomon, L. (1963). Hereditary multiple exostosis. J. Bone Joint Surg.45,292-304.","DOI":"10.1302\/0301-620X.45B2.292"},{"key":"2021042605191222400_REF51","doi-asserted-by":"crossref","unstructured":"St-Jacques, B., Hammerschmidt, M. and McMahon, A. P.(1999). Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev.13,2072-2086.","DOI":"10.1101\/gad.13.16.2072"},{"key":"2021042605191222400_REF52","doi-asserted-by":"crossref","unstructured":"Stickens, D., Clines, G., Burbee, D., Ramos, P., Thomas, S.,Hogue, D., Hecht, J. T., Lovett, M. and Evans, G. A.(1996). The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nat. Genet.14, 25-32.","DOI":"10.1038\/ng0996-25"},{"key":"2021042605191222400_REF53","doi-asserted-by":"crossref","unstructured":"Takei, Y., Ozawa, Y., Sato, M., Watanabe, A. and Tabata, T.(2004). Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development131,73-82.","DOI":"10.1242\/dev.00913"},{"key":"2021042605191222400_REF54","doi-asserted-by":"crossref","unstructured":"Tanaka, S., Kunath, T., Hadjantonakis, A. K., Nagy, A. and Rossant, J. (1998). Promotion of trophoblast stem cell proliferation by FGF4. Science282,2072-2075.","DOI":"10.1126\/science.282.5396.2072"},{"key":"2021042605191222400_REF55","doi-asserted-by":"crossref","unstructured":"Thomas, P. and Beddington, R. (1996). Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr. Biol.6,1487-1496.","DOI":"10.1016\/S0960-9822(96)00753-1"},{"key":"2021042605191222400_REF56","doi-asserted-by":"crossref","unstructured":"Wei, G., Bai, X., Gabb, M. M., Bame, K. J., Koshy, T. I., Spear,P. G. and Esko, J. D. (2000). Location of the glucuronosyltransferase domain in the heparan sulfate copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants. J. Biol. Chem.275,27733-27740.","DOI":"10.1074\/jbc.M002990200"},{"key":"2021042605191222400_REF57","doi-asserted-by":"crossref","unstructured":"Wilkinson, D. G., Bhatt, S. and Herrmann, B. G.(1990). Expression pattern of the mouse T gene and its role in mesoderm formation. Nature343,657-659.","DOI":"10.1038\/343657a0"},{"key":"2021042605191222400_REF58","doi-asserted-by":"crossref","unstructured":"Winnier, G., Blessing, M., Labosky, P. A. and Hogan, B. L.(1995). Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. 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