Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA.
Cold Spring Harb Perspect Med. 2024 Feb 1;14(2):a041286. doi: 10.1101/cshperspect.a041286.
Naturally occurring inherited retinal diseases (IRDs) in cats and dogs provide a rich source of potential models for human IRDs. In many cases, the phenotypes between the species with mutations of the homologous genes are very similar. Both cats and dogs have a high-acuity retinal region, the area centralis, an equivalent to the human macula, with tightly packed photoreceptors and higher cone density. This and the similarity in globe size to that of humans means these large animal models provide information not obtainable from rodent models. The established cat and dog models include those for Leber congenital amaurosis, retinitis pigmentosa (including recessive, dominant, and X-linked forms), achromatopsia, Best disease, congenital stationary night blindness and other synaptic dysfunctions, -associated retinopathy, and Stargardt disease. Several of these models have proven to be important in the development of translational therapies such as gene-augmentation therapies. Advances have been made in editing the canine genome, which necessitated overcoming challenges presented by the specifics of canine reproduction. Feline genome editing presents fewer challenges. We can anticipate the generation of specific cat and dog IRD models by genome editing in the future.
天然发生的遗传性视网膜疾病（IRDs）在猫和狗中为人类 IRDs 提供了丰富的潜在模型来源。在许多情况下，具有同源基因突变的物种之间的表型非常相似。猫和狗都有一个高敏视网膜区域，即中央凹，相当于人类的黄斑，具有紧密排列的光感受器和更高的锥体细胞密度。这一点以及与人类眼球大小的相似性意味着这些大型动物模型提供了无法从啮齿动物模型获得的信息。已建立的猫和狗模型包括莱伯先天性黑蒙、视网膜色素变性（包括隐性、显性和 X 连锁形式）、色盲、Best 病、先天性静止性夜盲症和其他突触功能障碍、相关视网膜病变和斯塔加特病。其中一些模型在基因增强疗法等转化疗法的发展中被证明是重要的。在编辑犬基因组方面取得了进展，这需要克服犬繁殖特定性带来的挑战。猫基因组编辑提出的挑战较少。我们可以预期在未来通过基因组编辑生成特定的猫和狗 IRD 模型。
