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Dominique Stickens, Ph.D.
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.
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| Dr. Stickens research |
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| 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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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and 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
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium, a European Commission
granted Network of Excellence for studying the pathology and genetics of bone tumors.
granted Network of Excellence for studying the pathology and genetics of bone tumors.
Dr. Stickens serves on the Scientific and Medical Advisory Board of the MHE Research Foundation
Research authored by Dr. Stickens
Click the tab and a window will appear.
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)
