Mice deficient in Ext2 lack heparan sulfate and develop exostoses
Abstract 2005 MHE Conference
Dominique Stickens1, Beverly M. Zak2¶, Nathalie Rougier1¶+,
Jeffrey D. Esko2 and Zena Werb1*
1Department of Anatomy, University of California, San Francisco, CA 94143-0452
2 Department of Cellular and Molecular Medicine, University of California, San Diego,
9500 Gilman Drive, La Jolla, CA, 92093-0687
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 1/3 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.
The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular
mechanisms underlying the development of exostoses.
Abstract 2005 MHE Conference
Dominique Stickens1, Beverly M. Zak2¶, Nathalie Rougier1¶+,
Jeffrey D. Esko2 and Zena Werb1*
1Department of Anatomy, University of California, San Francisco, CA 94143-0452
2 Department of Cellular and Molecular Medicine, University of California, San Diego,
9500 Gilman Drive, La Jolla, CA, 92093-0687
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 1/3 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.
The finding that haploinsufficiency triggers abnormal cartilage differentiation gives insight into the complex molecular
mechanisms underlying the development of exostoses.
| Dr. Dominque Stickens research |
| On September 30, 2007 during the FUNTASIA Research banquet Dr. Stickens was presented with the "REACH Research Award" along with CITATION from Borough of Brooklyn City of New York, Office of the President, Presented by the President Marty Markowitz. PROCLAMATION from New York State Senate, Presented by Senator Martin J. Golden. CERTIFICATE OF RECOGNITION in honor of their Commitment to the MHE Research Foundation from United States Congress U.S. House of Representatives, Presented by Congressman Vito J. Fossella. To read more about this event and view Dr. Sticken's speech Click Here |
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Dr. Stickens serves on the Scientific and Medical Advisory Board of the MHE Research Foundation
Research authored by Dr. Stickens
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List of Publications via PubMed
(NIH National Library of Medicine)
Research authored by Dr. Stickens
Click the tab and a window will appear.
List of Publications via PubMed
(NIH National Library of Medicine)
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| Photo's taken during the Third International MHE Research Conference |
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website, also linked for Patient Information on The Diseases Database a cross-referenced index of human disease, as well as the
Intute: health & life sciences a free online service providing access to the very best Web resources for education and research located in the UK
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