Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen

Dennis M. Marcus, Jacques G.H. Lasudry, James L. Carpenter, Jolene Windle, Kimberly A. Howes, Muayyad R. Al-Ubaidi, Wolfgang Baehr, Paul A. Overbeek, Ramon L. Font, Daniel Albert

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose. A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ('trilateral') were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. Methods. Formalin- fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. Results. Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. Conclusions. Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.

Original languageEnglish (US)
Pages (from-to)392-396
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number2
StatePublished - Feb 1 1996
Externally publishedYes

Fingerprint

Polyomavirus Transforming Antigens
Primitive Neuroectodermal Tumors
Transgenic Mice
alpha-Crystallin A Chain
Third Ventricle
Cerebral Aqueduct
Brain Neoplasms
Neoplasms
Luteinizing Hormone
Mesencephalon
Retinal Neoplasms
Brain Stem Neoplasms
Pinealoma
Cerebral Ventricles
Diencephalon
Vertebrate Photoreceptor Cells
Simian virus 40
Retinoblastoma
Nucleic Acid Regulatory Sequences
Viral Tumor Antigens

Keywords

  • brain tumors
  • retinoblastoma
  • SV40 T-antigen
  • transgenic animals
  • trilateral

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Marcus, D. M., Lasudry, J. G. H., Carpenter, J. L., Windle, J., Howes, K. A., Al-Ubaidi, M. R., ... Albert, D. (1996). Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen. Investigative Ophthalmology and Visual Science, 37(2), 392-396.

Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen. / Marcus, Dennis M.; Lasudry, Jacques G.H.; Carpenter, James L.; Windle, Jolene; Howes, Kimberly A.; Al-Ubaidi, Muayyad R.; Baehr, Wolfgang; Overbeek, Paul A.; Font, Ramon L.; Albert, Daniel.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 2, 01.02.1996, p. 392-396.

Research output: Contribution to journalArticle

Marcus, DM, Lasudry, JGH, Carpenter, JL, Windle, J, Howes, KA, Al-Ubaidi, MR, Baehr, W, Overbeek, PA, Font, RL & Albert, D 1996, 'Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen', Investigative Ophthalmology and Visual Science, vol. 37, no. 2, pp. 392-396.
Marcus DM, Lasudry JGH, Carpenter JL, Windle J, Howes KA, Al-Ubaidi MR et al. Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen. Investigative Ophthalmology and Visual Science. 1996 Feb 1;37(2):392-396.
Marcus, Dennis M. ; Lasudry, Jacques G.H. ; Carpenter, James L. ; Windle, Jolene ; Howes, Kimberly A. ; Al-Ubaidi, Muayyad R. ; Baehr, Wolfgang ; Overbeek, Paul A. ; Font, Ramon L. ; Albert, Daniel. / Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen. In: Investigative Ophthalmology and Visual Science. 1996 ; Vol. 37, No. 2. pp. 392-396.
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abstract = "Purpose. A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ('trilateral') were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. Methods. Formalin- fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. Results. Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. Conclusions. Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.",
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AU - Howes, Kimberly A.

AU - Al-Ubaidi, Muayyad R.

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