Glover Greta, Mueller Kaspar P, Söllner Christian, Neuhauss Stephan C F, Nicolson Teresa
Oregon Hearing Research Center and Vollum Institute, HHMI/Oregon Health & Science University, Portland, OR 97219, USA.
Mol Vis. 2012;18:2309-22. Epub 2012 Sep 5.
To characterize the expression pattern of cadherin 23 (cdh23) in the zebrafish visual system, and to determine whether zebrafish cdh23 mutants have retinal defects similar to those present in the human disease Usher syndrome 1D.
In situ hybridization and immunohistochemistry were used to characterize cdh23 expression in the zebrafish, and to evaluate cdh23 mutants for retinal degeneration. Visual function was assessed by measurement of the optokinetic response in cdh23 siblings and mutants.
We detected cdh23 mRNA expression in multiple nuclei of both the developing and adult central nervous system. In the retina, cdh23 mRNA was expressed in a small subset of amacrine cells, beginning at 70 h postfertilization and continuing through adulthood. No expression was detected in photoreceptors. The cdh23-positive population of amacrine cells was GABAergic. Examination of homozygous larvae expressing two different mutant alleles of cdh23-cdh23(tc317e) or cdh23(tj264a)-revealed no detectable morphological retinal defects or degeneration. In addition, the optokinetic response to moving gratings of varied contrast or spatial frequency was normal in both mutants.
Unlike in other vertebrates, cdh23 is not detectable in zebrafish photoreceptors. Instead, cdh23 is expressed by a small subset of GABAergic amacrine cells. Moreover, larvae with mutations in cdh23 do not exhibit any signs of gross retinal degeneration or dysfunction. The role played by cdh23 in human retinal function is likely performed by either a different gene or an unidentified cdh23 splice variant in the retina that is not affected by the above mutations.
表征钙黏蛋白23（cdh23）在斑马鱼视觉系统中的表达模式，并确定斑马鱼cdh23突变体是否具有与人类1D型Usher综合征中存在的视网膜缺陷相似的缺陷。
采用原位杂交和免疫组织化学方法表征cdh23在斑马鱼中的表达，并评估cdh23突变体的视网膜变性情况。通过测量cdh23同胞和突变体的视动反应来评估视觉功能。
我们在发育中和成年中枢神经系统的多个核中检测到cdh23 mRNA表达。在视网膜中，cdh23 mRNA在受精后70小时开始在一小部分无长突细胞中表达，并持续到成年期。在光感受器中未检测到表达。无长突细胞的cdh23阳性群体是γ-氨基丁酸能的。对表达cdh23的两个不同突变等位基因cdh23(tc317e)或cdh23(tj264a)的纯合幼虫的检查显示，未检测到明显的视网膜形态缺陷或变性。此外，两个突变体对不同对比度或空间频率的移动光栅的视动反应均正常。
与其他脊椎动物不同，在斑马鱼光感受器中未检测到cdh23。相反，cdh23由一小部分γ-氨基丁酸能无长突细胞表达。此外，cdh23突变的幼虫未表现出任何明显的视网膜变性或功能障碍迹象。cdh23在人类视网膜功能中所起的作用可能由视网膜中一个不同的基因或一个未鉴定的不受上述突变影响的cdh23剪接变体来执行。
