Peachey N S, Goto Y, Quiambao A B, al-Ubaidi M R
Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood, USA.
Vis Neurosci. 1995 May-Jun;12(3):513-22. doi: 10.1017/s0952523800008427.
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.
本研究评估了在转基因小鼠中，在光感受器特异性启动子控制下癌基因表达后小鼠的视网膜功能。在选择用于激发视杆或视锥介导成分的刺激条件下记录视网膜电图（ERG）。在一个转基因品系（MOT1）中，猴病毒40大肿瘤抗原在小鼠视蛋白启动子的控制下表达。MOT1小鼠视杆介导的ERG a波振幅呈现与年龄相关的下降。相比之下，从MOT1小鼠记录的视锥介导反应在长达四个月龄（测试的最大年龄）时仍保持正常。在第二个转基因品系（CMYC）中，大鼠c-myc基因在人光感受器间类视黄醇结合蛋白启动子的控制下表达。CMYC小鼠视锥介导反应迅速减少，视杆ERG a波逐渐丧失。对年轻的MOT1和CMYC小鼠获得的视杆ERG a波分析表明，视杆ERG异常反映了对视杆介导反应有贡献的视杆数量减少，而剩余视杆的反应特性保持正常。这些结果支持了癌基因的异常表达可能是某些形式的人类视杆和视锥-视杆营养不良的基础这一可能性。
