Persistent hyperplastic primary vitreous in transgenic mice expressing IE180 of the pseudorabies virus.
OBJECTIVE
Pseudorabies virus (PRV), a representative member of the alpha-herpesvirus family, causes nervous symptoms and ocular lesions, such as keratoconjunctivitis and retinal degeneration in piglets. The immediate-early protein IE180 of the PRV is known to be essential, not only in viral gene expression, but also in the cellular gene expression in host cells. The purpose of this study was to examine the effect of IE180 on the development of the mouse eye, by using transgenic technology.


METHODS
Transgenic mice expressing IE180 were generated and their eyes analyzed by histology, immunocytochemistry, and the bromodeoxyuridine cell proliferation assay.


RESULTS
A fibrovascular retrolental tissue analogous to persistent hyperplastic primary vitreous (PHPV) in humans was observed in a transgenic mouse line expressing IE180. The gross anatomy of the eye showed white pupils. Analysis of hematoxylin and eosin-stained sections revealed that the retrolental tissue adhered to the neuroretina, the inner nuclear and ganglion cell layers were disorganized, and rosettelike arrangements of dysplastic photoreceptor cells were present. Bromodeoxyuridine-positive cells were detected in the retrolental tissues of postnatal day (P)1, P7, and P14 mice. The retrolental mass in the P7 transgenic mouse was composed of melanocytes and endothelial cells, which were detected by a cocktail of antibodies against endoglin, CD31, and VEGF receptor-2.


CONCLUSIONS
The observation that the eye disease in transgenic mice is similar to that in PHPV in humans raises the possibility that expression of the immediate-early gene of alpha-herpesviruses may contribute to PHPV.
Taharaguchi
Satoshi
S
Laboratory of Animal Experiment for Disease Model, Institute of Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Yoshida
Kazuhiko
K
Tomioka
Yukiko
Y
Yoshino
Saori
S
Uede
Toshimitsu
T
Ono
Etsuro
E
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D011558:Herpesvirus 1, Suid; D006965:Hyperplasia; D017874:Immediate-Early Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D014822:Vitreous Body / Q000002:abnormalities* / Q000098:blood supply* / Q000473:pathology
D015415:Biomarkers; D017874:Immediate-Early Proteins; C047583:pseudorabies virus immediate early proteins