Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter

Muayyad R. Al-Ubaidi, Ramon L. Font, Alexander B. Quiambao, Mary J. Keener, Gregory I. Liou, Paul A. Overbeek, Wolfgang Baehr

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.

Original languageEnglish (US)
Pages (from-to)1681-1687
Number of pages7
JournalJournal of Cell Biology
Volume119
Issue number6
DOIs
StatePublished - Jan 1 1992

Fingerprint

Retinal Neoplasms
Simian virus 40
Viral Tumor Antigens
Brain Neoplasms
Transgenic Mice
Retinal Rod Photoreceptor Cells
Photoreceptor Cells
Transgenes
Retinal Cone Photoreceptor Cells
Opsins
Polyomavirus Transforming Antigens
Primitive Neuroectodermal Tumors
Synaptophysin
Vertebrate Photoreceptor Cells
Retinoblastoma
Antibodies
Oncogene Proteins
Embryonic Development
Cell Death
Embryonic Structures

ASJC Scopus subject areas

  • Cell Biology

Cite this

Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. / Al-Ubaidi, Muayyad R.; Font, Ramon L.; Quiambao, Alexander B.; Keener, Mary J.; Liou, Gregory I.; Overbeek, Paul A.; Baehr, Wolfgang.

In: Journal of Cell Biology, Vol. 119, No. 6, 01.01.1992, p. 1681-1687.

Research output: Contribution to journalArticle

Al-Ubaidi, Muayyad R. ; Font, Ramon L. ; Quiambao, Alexander B. ; Keener, Mary J. ; Liou, Gregory I. ; Overbeek, Paul A. ; Baehr, Wolfgang. / Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. In: Journal of Cell Biology. 1992 ; Vol. 119, No. 6. pp. 1681-1687.
@article{2615118910234411b234b5d3bfe2e1b5,
title = "Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter",
abstract = "We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.",
author = "Al-Ubaidi, {Muayyad R.} and Font, {Ramon L.} and Quiambao, {Alexander B.} and Keener, {Mary J.} and Liou, {Gregory I.} and Overbeek, {Paul A.} and Wolfgang Baehr",
year = "1992",
month = "1",
day = "1",
doi = "10.1083/jcb.119.6.1681",
language = "English (US)",
volume = "119",
pages = "1681--1687",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter

AU - Al-Ubaidi, Muayyad R.

AU - Font, Ramon L.

AU - Quiambao, Alexander B.

AU - Keener, Mary J.

AU - Liou, Gregory I.

AU - Overbeek, Paul A.

AU - Baehr, Wolfgang

PY - 1992/1/1

Y1 - 1992/1/1

N2 - We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.

AB - We have previously shown that postnatal expression of the viral oncoprotein SV40 T antigen in rod photoreceptors (transgene MOT1), at a time when retinal cells have withdrawn from the mitotic cycle, leads to photoreceptor cell death (Al-Ubaidi et al., 1992. Proc. Natl. Acad. Sci. USA. 89:1194-1198). To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development. The resulting construct, termed HIT1, was injected into mouse embryos and five transgenic mice lines were established. Mice heterozygous for HIT1 exhibited early bilateral retinal and brain tumors with varying degrees of incidence. Histopathological examination of the brain and eyes of three of the families showed typical primitive neuroectodermal tumors. In some of the bilateral retinal tumors, peculiar rosettes were observed, which were different from the Flexner-Wintersteiner rosettes typically associated with human retinoblastomas. The ocular and cerebral tumors, however, contained Homer-Wright rosettes, and showed varying degrees of immunoreactivity to antibodies against the neuronal specific antigens, synaptophysin and Leu7, but not to antibodies against photoreceptor specific proteins. Taken together, the results indicate that the specificity of the promoter used for T antigen and/or the time of onset of transgene expression determines the fate of photoreceptor cells expressing T antigen.

UR - http://www.scopus.com/inward/record.url?scp=0027074996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027074996&partnerID=8YFLogxK

U2 - 10.1083/jcb.119.6.1681

DO - 10.1083/jcb.119.6.1681

M3 - Article

VL - 119

SP - 1681

EP - 1687

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -