Department of Otorhinolaryngology, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands.
Department of Ophthalmology, Justus-Liebig-University, Friedrichstraβe 18, 35392, Gieβen, Germany.
Prog Retin Eye Res. 2015 Sep;48:137-59. doi: 10.1016/j.preteyeres.2015.04.004. Epub 2015 May 1.
Over the last decade, huge progress has been made in the understanding of the molecular mechanisms underlying inherited retinal dystrophy (IRD), as well as in the development and implementation of novel therapies, especially in the field of gene therapy. The use of mutant animal models, either naturally occurring or generated by genetic modification, have contributed greatly to our knowledge on IRD. Yet, these mutant animal models do not always mimic the retinal phenotype that is observed in humans with mutations in the orthologous gene, often due to species-specific characteristics of the retina, and/or diverse functions of the gene products in different species. In this manuscript, we compare general and ocular characteristics of a series of widely used vertebrate animal models, i.e. zebrafish, chicken, rodents, cats, dogs, sheep, pigs and monkeys, in terms of genetic architecture and sequence homology, methods to modify genomes, anatomy of the eye, and structural details of the retina. Furthermore, we present an overview of mutant vertebrate animal models that have been used to study or develop treatments for the various genetic subtypes of IRD, and correlate the suitability of these models to the specific characteristics of each animal. Herewith, we provide tools that will help to select the most suitable animal model for specific research questions on IRDs in the future, and thereby assist in an optimal use of animals and resources to further increase our understanding of inherited retinal dystrophies, and develop novel treatments for these disorders.
在过去的十年中，人们对遗传性视网膜营养不良（IRD）的分子机制有了更深入的了解，并且开发和实施了新的疗法，特别是在基因治疗领域。利用突变动物模型，无论是自然发生的还是通过基因修饰产生的，都极大地促进了我们对 IRD 的认识。然而，这些突变动物模型并不总是能模拟出与同源基因突变的人类患者中观察到的视网膜表型，这通常是由于视网膜在物种间存在特异性特征，以及/或者不同物种中基因产物的功能多样化。在本文中，我们比较了一系列广泛使用的脊椎动物模型（即斑马鱼、鸡、啮齿动物、猫、狗、绵羊、猪和猴子）的一般和眼部特征，包括遗传结构和序列同源性、基因组修饰方法、眼睛解剖结构以及视网膜的结构细节。此外，我们还概述了已用于研究或开发各种遗传性视网膜营养不良遗传亚型治疗方法的突变脊椎动物模型，并将这些模型的适用性与每种动物的特定特征相关联。通过本文，我们提供了一些工具，这将有助于未来选择最适合特定 IRD 研究问题的动物模型，从而有助于优化动物和资源的利用，以进一步加深我们对遗传性视网膜营养不良的认识，并开发这些疾病的新疗法。
