Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter

Sugaya, Makoto ; Watanabe, Takahiro ; Yang, Aparche ; Starost, Matthew F. ; Kobayashi, Hisataka ; Atkins, April M. ; Borris, Debra L. ; Hanan, Elisabeth A. ; Schimel, Daniel and Bryant, Mark A. , et al. (2005) In Blood 105(6). p.2356-2363
Abstract

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 ussue. 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... (More)

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 ussue. 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
in
Blood
volume
105
issue
6
pages
2356 - 2363
publisher
American Society of Hematology
external identifiers
  • pmid:15536152
  • scopus:20144383238
ISSN
0006-4971
DOI
10.1182/blood-2004-08-3364
language
English
LU publication?
no
id
c9b137ab-934a-4573-856a-ad43f936117b
date added to LUP
2019-09-18 14:27:46
date last changed
2024-04-02 18:24:04
@article{c9b137ab-934a-4573-856a-ad43f936117b,
  abstract     = {{<p>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 ussue. 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<sup>+</sup> 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.</p>}},
  author       = {{Sugaya, Makoto and Watanabe, Takahiro and Yang, Aparche and Starost, Matthew F. and Kobayashi, Hisataka and Atkins, April M. and Borris, Debra L. and Hanan, Elisabeth A. and Schimel, Daniel and Bryant, Mark A. and Roberts, Nicole and Skobe, Mihaela and Staskus, Katherine A. and Kaldis, Philipp and Blauvelt, Andrew}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{6}},
  pages        = {{2356--2363}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter}},
  url          = {{http://dx.doi.org/10.1182/blood-2004-08-3364}},
  doi          = {{10.1182/blood-2004-08-3364}},
  volume       = {{105}},
  year         = {{2005}},
}