P23H Rhodopsin Mutant Swine Model of Reninitis Pigmentosa

描述（由申请人提供）：视网膜变性是西方世界失明的主要原因，视网膜色素变性（RP）是成人遗传性视力丧失的最常见原因。尽管RP的遗传基础已经被很好地探索，但由于这组疾病的突变异质性，将这种见解转化为成功的基因治疗一直受到阻碍。除了基因治疗，我们和其他人正在探索替代治疗方法，采用干细胞治疗的最新进展，以及视网膜假体，生物工程和药理学。这些共同持有的承诺，成功的神经重建RP。 使用单细胞核移植的方法，我们在密苏里-哥伦比亚大学的国家猪资源研究中心生产了6只携带突变Pro23His（P23H）人视紫红质转基因的NIH cc单倍型雄性小型猪（迷你猪）。我们的初步数据表明，这些创始人表现出RP的电生理表型特征。由于P23 H是最常见的常染色体显性突变负责RP在人，我们建议建立一个殖民地，并表征三个独立的转基因系的这种新的小型猪模型的感光细胞变性。虽然在此应用的时间范围之外，但在不久的将来，我们和视觉界可以将其用于新的治疗干预。 公共卫生相关性：使用单细胞核移植的方法，我们在密苏里-哥伦比亚大学的国家猪资源研究中心生产了6只携带突变Pro23His（P23H）人视紫红质转基因的NIH cc单倍型雄性小型猪（迷你猪）。我们的初步数据表明，这些创始人表现出视网膜色素变性（RP）的电生理表型特征。由于P23 H是最常见的常染色体显性突变，负责RP在人类中，我们建议建立一个殖民地，并表征三个独立的转基因系的这种新的小型猪模型的感光细胞变性为未来的治疗干预。

DESCRIPTION (provided by applicant): Retinal degeneration is a leading cause of blindness in the Western world and retinitis pigmentosa (RP) is the most common cause of hereditary visual loss in adult life. Although the genetic basis of RP has been well explored, the translation of this insight into successful genetic therapy has been hindered because of the mutational heterogeneity that underlies this group of diseases. In addition to gene therapy, we and others are exploring alternative therapeutic approaches employing recent advances in stem cell therapy, as well as the retinal prosthesis, bioengineering and pharmacology. Together these hold the promise for successful neural reconstitution in RP. Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of RP. Since P23H is the most common autosomal dominant mutation responsible for RP in man, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration. While outside the time frame of this application, in the near future it can be used by us and the vision community for novel therapeutic interventions. PUBLIC HEALTH RELEVANCE: Using the method of single cell nuclear transfer, we produced six male miniature swine (mini-swine) on a NIH cc haplotype carrying a mutant Pro23His (P23H) human rhodopsin transgene at the National Swine Resource Research Center at the University of Missouri-Columbia. Our preliminary data show that these founders exhibited an electrophysiologic phenotype characteristic of retinitis pigmentosa (RP). Since P23H is the most common autosomal dominant mutation responsible for RP in humans, we propose to establish a colony and characterize three independent transgenic lines of this new mini-swine model of photoreceptor degeneration for future therapeutic interventions.