PMID- 15536152
OWN - NLM
STAT- MEDLINE
DCOM- 20060707
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 6
DP  - 2005 Mar 15
TI  - Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the 
      control of the VEGFR-3 promoter.
PG  - 2356-63
AB  - 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.
FAU - Sugaya, Makoto
AU  - Sugaya M
AD  - Dermatology Branch, National Cancer Institute, Office of Research Services, 
      Division of Veterinary Resources, Bethesda, MD, USA.
FAU - Watanabe, Takahiro
AU  - Watanabe T
FAU - Yang, Aparche
AU  - Yang A
FAU - Starost, Matthew F
AU  - Starost MF
FAU - Kobayashi, Hisataka
AU  - Kobayashi H
FAU - Atkins, April M
AU  - Atkins AM
FAU - Borris, Debra L
AU  - Borris DL
FAU - Hanan, Elisabeth A
AU  - Hanan EA
FAU - Schimel, Daniel
AU  - Schimel D
FAU - Bryant, Mark A
AU  - Bryant MA
FAU - Roberts, Nicole
AU  - Roberts N
FAU - Skobe, Mihaela
AU  - Skobe M
FAU - Staskus, Katherine A
AU  - Staskus KA
FAU - Kaldis, Philipp
AU  - Kaldis P
FAU - Blauvelt, Andrew
AU  - Blauvelt A
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20041109
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cyclin D)
RN  - 0 (Cyclins)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
SB  - IM
MH  - Animals
MH  - Cell Nucleus
MH  - Cyclin D
MH  - Cyclins/*genetics/metabolism
MH  - Edema/genetics/metabolism/pathology
MH  - Endothelium, Lymphatic/metabolism/pathology
MH  - Erythrocytes/metabolism/pathology
MH  - Herpesvirus 8, Human/enzymology/*genetics
MH  - Humans
MH  - Lung/metabolism/pathology
MH  - Lymphatic Diseases/*genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Promoter Regions, Genetic/*genetics
MH  - Sarcoma, Kaposi/genetics/metabolism/pathology
MH  - Skin Abnormalities/genetics/pathology
MH  - Transgenes/genetics
MH  - Vascular Endothelial Growth Factor Receptor-3/*genetics
MH  - Viral Proteins/*genetics/metabolism
EDAT- 2004/11/13 09:00
MHDA- 2006/07/11 09:00
CRDT- 2004/11/13 09:00
PHST- 2004/11/13 09:00 [pubmed]
PHST- 2006/07/11 09:00 [medline]
PHST- 2004/11/13 09:00 [entrez]
AID - S0006-4971(20)45737-4 [pii]
AID - 10.1182/blood-2004-08-3364 [doi]
PST - ppublish
SO  - Blood. 2005 Mar 15;105(6):2356-63. doi: 10.1182/blood-2004-08-3364. Epub 2004 Nov 
      9.