GENETIC MODEL OF EYE DISEASE

眼部疾病的遗传模型

• 批准号: 3267101
• 负责人: Robert M Petters
• 金额: $ 13.7万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3267101
• 关键词: animal breeding; biopsy; genetic models; genetically modified animals; model design /development; molecular pathology; point mutation; polymerase chain reaction; retinitis pigmentosa; rhodopsin; swine

This project aims at producing a genetic model in the pig for investigating the mechanisms by which mutations of the rhodopsin gene lead to photoreceptor death and widespread retinal degeneration in humans. Retinitis pigmentosa (RP) is a heterogeneous group of degenerative disorders that primarily affect photoreceptors and the retinal pigment epithelium. However, the clinical course of the different forms of RP follows a similar well-defined pattern. It is known that these disorders may be caused by mutations at various loci within the genome involving separate genes. Accordingly, the different hereditary types of RP are not produced by an identical defect but the similar end results imply that they share some common steps in pathogenesis. More than twenty point mutations of the rhodopsin gene have been identified in patients with autosomal dominant RP. However, the relationship between these mutations and the mechanisms of RP is not known. Specifically, through what mechanisms do mutations in the rhodopsin gene, which is a rod-specific gene, cause widespread photoreceptor degeneration, including the cones? Although mutations of the rhodopsin gene cannot account for all the known hereditary types of RP, they offer a prototype for studying the pathogenesis of RP. Preliminary experiments on transgenic mice have indicated that a mutant rhodopsin 'transgene' causes photoreceptor dysfunction. If similar transgenic pigs can be generated, it will provide a better model for studying the disease process of RP because the pig eye resembles the human eye much more closely than the mouse does. Whereas the RP disease process in mice is expected not to parallel closely that of the human, it should be very similar in the pig. If transgenic pigs develop RP, they will be useful for studying the pathogenesis as well as possible treatments of RP.

该项目的目的是在猪中建立一个遗传模型， 研究视紫红质基因突变 导致光感受器死亡和广泛视网膜变性 人类 视网膜色素变性（RP）是一组异质性的， 主要影响光感受器的退行性疾病， 视网膜色素上皮 然而， 不同形式的RP遵循类似的明确定义的模式。 是 已知这些疾病可能由不同基因座的突变引起， 基因组中的不同基因。 因此，不同的 遗传型RP不是由相同的缺陷产生的，而是由 类似的最终结果意味着它们在以下方面具有一些共同的步骤： 发病机制 视紫红质基因的二十多个点突变 已在常染色体显性遗传RP患者中发现。 然而，在这方面， 这些突变与RP机制之间的关系不是 知道的 具体来说，基因突变是通过什么机制发生的？ 视紫红质基因是视杆细胞特异性基因， 包括视锥细胞在内的光感受器退化虽然突变的 视紫红质基因不能解释所有已知的遗传类型， 为研究RP的发病机制提供了原型。 对转基因小鼠的初步实验表明，突变体 视紫红质'转基因'导致光感受器功能障碍。 如果类似 转基因猪可以产生，它将提供一个更好的模型， 研究RP的发病过程，因为猪眼类似于 人类的眼睛比老鼠看得更近。 而RP病 小鼠的过程预计不会与人类的过程密切平行， 猪的情况应该很相似 如果转基因猪出现RP， 将有助于研究发病机制，以及可能的 RP的治疗。