Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter
(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)
- author
- publishing date
- 2005-03-15
- 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}}, }