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Functional consequences of oncogene-induced photoreceptor degeneration in transgenic mice

Published online by Cambridge University Press:  02 June 2009

Neal S. Peachey ,
Yoshinobu Goto ,
Alexander B. Quiambao  and
Muayyad R. Al-Ubaidi
Neal S. Peachey
Affiliation:
Edward J. Hines VA Hospital, Hines Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood
Yoshinobu Goto
Affiliation:
Edward J. Hines VA Hospital, Hines Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood
Alexander B. Quiambao
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago
Muayyad R. Al-Ubaidi
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine, Chicago
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Abstract

This study evaluated retinal function in mice following the expression of oncogenes under the control of photoreceptor-specific promoters in transgenic mice. Electroretinograms (ERGs) were recorded under stimulus conditions chosen to elicit rod- or cone-mediated components. In one transgenic line (MOT1), the simian virus 40 large tumor antigen was expressed under the control of the mouse opsin promoter. MOT1 mice exhibited an age-related decline in the amplitude of the rod-mediated ERG a-wave. In comparison, cone-mediated responses recorded from MOT1 mice remained normal up to four months of age, the oldest age tested. In the second transgenic line (CMYC), the rat c-myc gene was expressed under control of the human interphotoreceptor-retinoid binding protein promoter. CMYC mice exhibited a rapid reduction of cone-mediated responses and a gradual loss of the rod ERG a-wave. Analysis of rod ERG a-waves obtained from young MOT1 and CMYC mice indicated that the rod ERG abnormalities reflect a reduction in the number of rods contributing to the response with the retention of normal response properties in rods that remain. These results support the possibility that aberrant expression of oncogenes may underlie some forms of human rod and cone-rod dystrophy.

Keywords

ElectroretinogramOncogenePhotoreceptorsRetinal DegenerationTransgenic mice
Type
Research Articles
Information
Visual Neuroscience , Volume 12 , Issue 3 , May 1995 , pp. 513 - 522
Copyright
Copyright © Cambridge University Press 1995

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References

Al-Ubaidi, M.R., Hollyfield, J.G., Overbeek, P.A. & Baehr, W. (1992). Photoreceptor degeneration induced by the expression of simian virus 40 large tumor antigen in the retina of transgenic mice. Proceedings of the National Academy of Sciences of the U.S.A. 89, 1194–1198.CrossRefGoogle ScholarPubMed
Al-Ubaidi, M.R., Quiambao, A.B., Myers, K.M. & Hollyfield, J.G. (1993). Expression of an oncogene causes slowly progressing retinal degeneration. Investigative Ophthalmology and Visual Science 34, 769. (ARVO Abstracts).Google Scholar
Baetge, E.E., Behringer, R.R., Messing, A., Brinster, R.L. & Palmiter, R.D. (1988). Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina. Proceedings of the National Academy of Sciences of the U.S.A. 85, 3648–3652.CrossRefGoogle ScholarPubMed
Bishop, J.M. (1991). Molecular themes in oncogenesis. Cell 64, 235–248.CrossRefGoogle ScholarPubMed
Blackwood, E.M. & Eisenman, R.N. (1991). Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251, 1211–1217.CrossRefGoogle Scholar
Breton, M.E., Schueller, A.W., Lamb, T.D. & Pugh, E.N. Jr., (1994). Analysis of ERG a-wave amplification and kinetics in terms of the G-protein cascade of phototransduction. Investigative Ophthalmology and Visual Science 35, 295–309.Google Scholar
Butel, J.S. (1986). SV40 large T-antigen: Dual oncogene. Cancer Surveys 5, 343–365.Google ScholarPubMed
Carr, R.E., Ripps, H., Siegel, I.M. & Weale, R.A. (1966). Rhodopsin and the electrical activity of the retina in congenital night blindness. Investigative Ophthalmology 5, 497–507.Google ScholarPubMed
Carter-Dawson, L.D. & La Vail, M.M. (1979 a). Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy. Journal of Comparative Neurology 188, 245–262.CrossRefGoogle ScholarPubMed
Carter-Dawson, L.D. & La Vail, M.M. (1979 b). Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine. Journal of Comparative Neurology 188, 263–272.CrossRefGoogle ScholarPubMed
Chen, J., Makino, C.L., Peachey, N.S., Baylor, D.A. & Simon, M.I. (1995). Mechanisms of rhodopsin inactivation in vivo as revealed by a C-terminal truncation mutant. Science 267, 374–377.Google Scholar
Clark, R.F. & Goate, A.M. (1993). Molecular genetics of Alzheimer's disease. Archives of Neurology 50, 1164–1172.CrossRefGoogle ScholarPubMed
DeCaprio, J.A., Ludlow, J.W., Figge, J., Shew, J., Huang, C., Lee, W., Marsilio, E., Paucha, E. & Livingston, D.M. (1988). SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275–283.CrossRefGoogle ScholarPubMed
Dornreiter, I., Hoss, A., Arthur, A.K. & Fanning, E. (1990). SV40 T antigen binds directly to the large subunit of purified DNA polymerase alpha. EMBO Journal 9, 3329–3336.CrossRefGoogle Scholar
Dryja, T.P., McGee, T.L., Reichel, E., Hahn, L.B., Cowley, G.S., Yandell, D.W., Sandberg, M.A. & Berson, E.L. (1990). A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343, 364–366.CrossRefGoogle ScholarPubMed
Erickson, P.A., Guerin, C.J. & Fisher, S.K. (1990). Tritiated uridine labeling of the retina: changes after retinal detachment. Experimental Eye Research 51, 153–158.CrossRefGoogle ScholarPubMed
Evan, G.I., Wyllie, A.H., Gilbert, C.S., Littlewood, T.D., Land, H., Brooks, M., Waters, C.M., Penn, L.Z. & Hancock, D.C. (1992). Induction of apoptosis in fibroblasts by c-myc protein. Cell 69, 119–128.CrossRefGoogle ScholarPubMed
Ewen, M.E., Ludlow, J.W., Marsilio, E., DeCaprio, J.A., Millikan, R.C., Cheng, S.H., Paucha, E. & Livingston, D.M. (1989). An N-terminal transformation-governing sequence of SV40 large T antigen contributes to the binding of both p110Rb and a second cellular protein, p120. Cell 58, 257–267.CrossRefGoogle Scholar
Fedderson, R.M., Ehlenfeldt, R., Yunis, W.S., Clark, H.B. & Orr, H.T. (1992). Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron 9, 955–966.CrossRefGoogle Scholar
Fishman, G.A. & Sokol, S. (1990). Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway. San Francisco, CA: American Academy of Ophthalmology.Google Scholar
Goto, Y., Peachey, N.S., Ripps, H. & Naash, M.I. (1995). Functional abnormalities in transgenic mice expressing a mutant rhodopsin gene. Investigative Ophthalmology and Visual Science 36, 62–71.Google ScholarPubMed
Gu, W., Bhatia, K., Magrath, I.T., Dang, C.V. & Dalla-Favera, R. (1994). Binding and suppression of the myc transcriptional activation domain by p107. Science 264, 251–254.CrossRefGoogle ScholarPubMed
Hammang, J.P., Behringer, R.R., Baetge, E.E., Palmiter, R.D., Brinster, R.L. & Messing, A. (1993). Oncogene expression in retinal horizontal cells of transgenic mice results in a cascade of neurodegeneration. Neuron 10, 1197–1202.CrossRefGoogle Scholar
Hanahan, D. (1988). Dissecting multistep tumorigenesis in transgenic mice. Annual Review of Genetics 22, 479–519.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1990). A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. Visual Neuroscience 5, 379–387.CrossRefGoogle ScholarPubMed
Hood, D.C. & Birch, D.G. (1993). Human cone receptor activity: The leading edge of the a-wave and models of receptor activity. Visual Neuroscience 10, 857–871.CrossRefGoogle Scholar
Hood, D.C. & Birch, D.G. (1994). Rod phototransduction in retinitis pigmentosa: Estimation and interpretation of parameters derived from the rod a-wave. Investigative Ophthalmology and Visual Science 35, 2948–2961.Google ScholarPubMed
Hood, D.C., Shady, S. & Birch, D.G. (1993). Heterogeneity in retinal disease and the computational model of the human-rod response. Journal of the Optical Society of America A 10, 1624–1630.CrossRefGoogle ScholarPubMed
Huang, P.C., Gaitin, A.E., Hao, Y., Petters, R.M. & Wong, F. (1993). Cellular interactions implicated in the mechanism of photoreceptor degeneration in transgenic mice expressing a mutant rhodopsin gene. Proceedings of the National Academy of Sciences of the U.S.A. 90, 8484–8488.CrossRefGoogle ScholarPubMed
Jacobs, G.H., Neitz, J. & IIDeegan, J.F. (1991). Retinal receptors in rodents maximally sensitive to ultraviolet light. Nature 353, 655–656.CrossRefGoogle ScholarPubMed
Lamb, T.D. & Pugh, E.N. Jr., (1992). A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. Journal of Physiology 449, 719–758.CrossRefGoogle ScholarPubMed
Lane, D.P. & Crawford, L.V. (1979). T antigen is bound to a host protein in SV40–transformed cells. Nature 278, 261–263.CrossRefGoogle ScholarPubMed
Luscher, B. & Eisenman, R.N. (1990). New light on Myc and Myb. Part I. Myc. Gene Development 4, 2025–2035.CrossRefGoogle ScholarPubMed
Naash, M.I., Hollyfield, J.G., Al-Ubaidi, M.R. & Baehr, W. (1993). Simulation of human autosomal dominant retinitis pigmentosa in transgenic mice expressing a mutated murine opsin gene. Proceedings of the National Academy of Sciences of the U.S.A. 90, 5499–5503.CrossRefGoogle ScholarPubMed
Overbeek, P.A., Chepelinsky, A.B., Khillan, J.S., Piatigorsky, J. & Westphal, H. (1985). Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A crystallin promoter in transgenic mice. Proceedings of the National A cademy of Sciences of the U.S.A. 82, 7815–7819.CrossRefGoogle ScholarPubMed
Peachey, N.S., Fishman, G.A., Kilbride, P.E., Alexander, K.R., Keehan, K.M. & Derlacki, D.J. (1990). A form of congenital stationary night blindness with apparent defect of rod phototransduction. Investigative Ophthalmology and Visual Science 31, 237–246.Google ScholarPubMed
Peachey, N.S., Goto, Y., Al-Ubaidi, M.R. & Naash, M.I. (1993). Properties of the mouse cone-mediated electroretinogram during light adaptation. Neuroscience Letters 162, 9–11.CrossRefGoogle ScholarPubMed
Penn, R.D. & Hagins, W.A. (1969). Signal transmission along retinal rods and the origin of the electroretinographic a-wave. Nature 223, 201–205.CrossRefGoogle ScholarPubMed
Shields, J.A. & Shields, C.A. (1992). Intraocular Tumors: A Text and Atlas. Philadelphia, PA: W.B. Saunders Company.Google Scholar
Smith, S.B. & Hamasaki, D.I. (1994). Electroretinographic study of the C57BL/6–mivit/mivit mouse model of retinal degeneration. Investigative Ophthalmology and Visual Science 35, 3119–3123.Google ScholarPubMed
Szel, A., Rohlich, P., Caffe, A.R., Juliusson, B., Aguirre, G. & van Veen, T. (1992). Unique topographic separation of two spectral classes of cones in the mouse retina. Journal of Comparative Neurology 325, 327–342.CrossRefGoogle ScholarPubMed
Wagner, S. & Knippers, R. (1990). An SV40 large T antigen binding site in the cellular genome is part of a cis-acting transcriptional element. Oncogene 5, 353–359.Google ScholarPubMed
Windle, J.J., Albert, D.M., O'Brien, J.M., Marcus, D.M., Disteche, C.M., Bernards, P. & Mellon, P. (1990). Retinoblastoma in transgenic mice. Nature 343, 665–669.CrossRefGoogle ScholarPubMed