Functional consequences of oncogene-induced photoreceptor degeneration in transgenic mice.
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.
Peachey
N S
NS
Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood, USA.
Goto
Y
Y
Quiambao
A B
AB
al-Ubaidi
M R
MR
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D003623:Dark Adaptation; D004596:Electroretinography; D015870:Gene Expression; D016259:Genes, myc; D008027:Light; D051379:Mice; D008822:Mice, Transgenic; D010786:Photoreceptor Cells / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D000952:Antigens, Polyomavirus Transforming; D016271:Proto-Oncogene Proteins c-myc