Van Epps H A, Yim C M, Hurley J B, Brockerhoff S E
Department of Biochemistry, Box 357350, University of Washington, Seattle, WA 98105, USA.
Invest Ophthalmol Vis Sci. 2001 Mar;42(3):868-74.
To characterize the retinal physiology of the zebrafish visual mutant no optokinetic response c (nrc) and to identify the genetic map position of the nrc mutation.
Electroretinograms were recorded from wild-type and nrc zebrafish larvae between 5 to 6 days postfertilization. Responses to flash stimuli, On and Off responses to prolonged light stimuli, and responses to flash stimuli with constant background illumination were characterized. The glutamate agonist, 2-amino-4-phosphonobutyric acid (APB) was used to examine the photoreceptor specific a-wave component of the electroretinogram. Amplified fragment length polymorphism methodology was used to place the nrc mutation on the zebrafish genomic map.
nrc and wild-type zebrafish larvae 5 to 6 days postfertilization have similar threshold responses to light, but the b-wave of the nrc electroretinogram is significantly delayed and reduced in amplitude. On and Off responses of nrc larvae to prolonged light have multiple oscillations that do not occur in normal zebrafish larvae after 5 days postfertilization. Analysis of the b-wave demonstrated a light adaptation defect in nrc that causes saturation at background light levels approximately 1 order of magnitude less than those with wild-type larvae. Application of the glutamate analog, APB, uncovered the photoreceptor component of the electroretinogram and revealed a light adaptation defect in nrc photoreceptors. The nrc mutation was placed approximately 0.2 cM from sequence length polymorphism marker Z7504 on linkage group 10.
The zebrafish mutant nrc is a possible model for human retinal disease. nrc has defects in photoreceptor synaptic transmission and light adaptation. The nrc mutant phenotype shows striking similarities with phenotypes of dystrophin glycoprotein complex mutants, including patients with Duchenne/Becker muscular dystrophy. Localization of the nrc mutation now makes it possible to evaluate candidate genes and clone the nrc gene.
描述斑马鱼视觉突变体无视动反应c（nrc）的视网膜生理学特征，并确定nrc突变的遗传图谱位置。
在受精后5至6天，记录野生型和nrc斑马鱼幼虫的视网膜电图。对闪光刺激的反应、对长时间光刺激的开和关反应以及在恒定背景光照下对闪光刺激的反应进行了特征描述。使用谷氨酸激动剂2-氨基-4-磷酸丁酸（APB）来检测视网膜电图中光感受器特异性的a波成分。采用扩增片段长度多态性方法将nrc突变定位到斑马鱼基因组图谱上。
受精后5至6天的nrc和野生型斑马鱼幼虫对光的阈值反应相似，但nrc视网膜电图的b波明显延迟且幅度减小。nrc幼虫对长时间光的开和关反应有多次振荡，而正常斑马鱼幼虫在受精后5天之后不会出现这种情况。对b波的分析表明nrc存在光适应缺陷，导致在背景光水平下饱和，其背景光水平比野生型幼虫低约1个数量级。应用谷氨酸类似物APB揭示了视网膜电图的光感受器成分，并显示nrc光感受器存在光适应缺陷。nrc突变位于第10连锁群上，与序列长度多态性标记Z7504相距约0.2 cM。
斑马鱼突变体nrc可能是人类视网膜疾病的一个模型。nrc在光感受器突触传递和光适应方面存在缺陷。nrc突变体表型与肌营养不良糖蛋白复合体突变体的表型有显著相似之处，包括杜氏/贝克型肌营养不良症患者。nrc突变的定位现在使得评估候选基因和克隆nrc基因成为可能。
