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More about Cardiovascular Biology Research Program
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Research Interests Our interest in endothelial cells developed from our previous studies of mice with global deficiency of T-synthase (T-syn-/-), a critical glycosyltransferase for biosynthesis of core 1-derived 2 O-glycans. The T-syn-/- mice developed unexpected abnormal angiogenesis with brain hemorrhage that was fatal at embryonic day 14. To identify whether O-glycans in endothelial cells are required for angiogenesis, we have developed mice lacking T-synthase specifically in endothelial cells or in perivascular tissues. We are breeding transgenic mice expressing T-synthase specifically in endothelial cells with T-syn-/- mice to determine whether endo-thelial-cell expression of T-synthase will rescue defective angiogenesis. We have also developed endothelial cell lines derived from T-syn-/- mice to explore the potential mechanisms for O-glycan-dependent angiogenesis. Both core 1- and core 3-derived O-glycans are found in gastrointestinal tracts, which constitute the major structural components of intestinal mucus. To study the role of core 1-derived O-glycans in these tissues, we developed intestinal epithelial cell-specific T-synthase-deficient mice (Epi T-syn-/-). To investigate the role of core 3-derived O-glycans, we developed mice with deficiency of core 3 b1,4-N-acetylglucosaminyltransferase (C3GnT-/-), an enzyme controlling the synthesis of core 3-derived O-glycans. We have also generated mice lacking both core 1- and core 3-derived O-glycans by breeding the Epi T-syn-/- and C3GnT -/- mice. These mouse models develop significant defects in intestinal function. We are now characterizing the phenotypes of these mouse models and delineating the mechanisms that underlie the phenotypes. Joined OMRF Scientific Staff in 2002. Mailing Address
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