| 1213 Elucidating the role of Alk1 in Hereditary Hemorrhagic Telangiectasia (HHT) | ||
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K. YO, Y.J. LEE, P.S. OH, and S. CHA, University of Florida, Gainesville, USA Objective: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant disorder with distinct oral manifestations including hemorrhagic vesicles, nodules, papules and ulcers on gingival tissue, and telangiectases (vascular lesion caused by direct connections of arterioles and venules without intervening capillaries) on the tongue. It is critical for a dentist to recognize oral manifestations of HHT because of potential hemorrhage during dental procedures. Types of HHT known in humans include: HHT1 and HHT2, which are caused by mutations in endoglin (Eng) or activin receptor-like kinase-1 (Alk1) gene, respectively. Restricted expression of Alk1 in arterial endothelium indicates that Alk1 may play a pivotal role in the maturation and stabilization of arterial vessels. This study is to investigate if Alk1 is necessary and sufficient for arteriogenesis. Methods: Alk1-transgenic mice, overexpressing Alk1 in the entire vascular endothelium under a pan-endothelial cell promoter, Tie2, with a Flag-tag, were generated by standard protocol. Two out of 23 offspring were established as a transgenic line for Alk1 by genomic PCR analysis and characterized for the roles of Alk1. Gene expression was confirmed by RT-PCR despite weak protein expression of Alk1 or Flag. Results: Out of a total of 69 Tg-positive-adult mice examined, 11 mice exhibited the splenic hemorrhage phenotype. There were no other apparent vascular malformations. These results indicate either a low level of transgenic Alk1 expression or insufficiency of Alk1 in causing transmorphogenesis of veins to artery-like vessels. Conclusion: Potential reasons for the results include: first, requirement for other essential molecules for Alk1-mediated-signaling; second, the transgene expression regulated by copy number and insertion location in the chromosome; third, requirement for stronger promoter/enhancer element. Thorough understanding of Alk1 in arteriogenesis will ameliorate the implication of HHT in dental practice as to how patients with this disorder can be identified and properly treated without complications. Supported by American-Heart-Association | ||
| Seq #129 - Clinical Diseases and Pathogenesis 3:30 PM-4:45 PM, Thursday, March 22, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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