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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2356-2363. Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-08-3364. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3364v1 105/6/2356    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sugaya, M. Articles by Blauvelt, A. Search for Related Content PubMed PubMed Citation Articles by Sugaya, M. Articles by Blauvelt, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter Makoto Sugaya, Takahiro Watanabe, Aparche Yang, Matthew F. Starost, Hisataka Kobayashi, April M. Atkins, Debra L. Borris, Elisabeth A. Hanan, Daniel Schimel, Mark A. Bryant, Nicole Roberts, Mihaela Skobe, Katherine A. Staskus, Philipp Kaldis, and Andrew Blauvelt From the Dermatology Branch, National Cancer Institute, Office of Research Services, Division of Veterinary Resources, Metabolism Branch, National Cancer Institute, and Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD; Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY; Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN; and Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD. Kaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Danussi, P. Spessotto, A. Petrucco, B. Wassermann, P. Sabatelli, M. Montesi, R. Doliana, G. M. Bressan, and A. Colombatti Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature Mol. Cell. Biol., June 15, 2008; 28(12): 4026 - 4039. [Abstract] [Full Text] [PDF]

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