title: Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice.
abstract: Expression of the viral oncogene encoding the simian virus 40 (SV40) large tumor antigen (T antigen) typically promotes tumorigenesis in mammalian cells. To generate transgenic mice that express T antigen in rod photoreceptors, a chimeric construct consisting of a mouse opsin promoter fragment fused to the coding region of SV40 T antigen was generated. Expression of T antigen in the transgenic retina began at early stages of postnatal development concomitant with expression of endogenous opsin. Instead of inducing hyperplasia or tumor formation, T-antigen expression caused a rapidly progressing photoreceptor degeneration. The degeneration was accompanied by sustained DNA synthesis in photoreceptor cells, as evidenced by incorporation of [3H]thymidine and by the appearance of mitotic figures at postnatal day 10, a stage when nontransgenic photoreceptor cells are postmitotic and quiescent. Although transgenic photoreceptor cells undergo S phase and enter mitosis, the consequences of T-antigen expression are not proliferation and tumorigenesis but proliferation and cell death.
authors.affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: M R
authors.initials: MR
authors.lastname: al-Ubaidi
authors.forename: J G
authors.initials: JG
authors.lastname: Hollyfield
authors.forename: P A
authors.initials: PA
authors.lastname: Overbeek
authors.forename: W
authors.initials: W
authors.lastname: Baehr
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D001483:Base Sequence; D005136:Eye Proteins / Q000235:genetics; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010786:Photoreceptor Cells / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000473:pathology* / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D017299:Rod Opsins; D013539:Simian virus 40 / Q000235:genetics*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D005136:Eye Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017299:Rod Opsins