Humphries M M, Rancourt D, Farrar G J, Kenna P, Hazel M, Bush R A, Sieving P A, Sheils D M, McNally N, Creighton P, Erven A, Boros A, Gulya K, Capecchi M R, Humphries P
Wellcome Ocular Genetics Unit, Genetics Department, Trinity College, Dublin, Ireland.
Nat Genet. 1997 Feb;15(2):216-9. doi: 10.1038/ng0297-216.
Retinitis pigmentosa (RP) represents the most common mendelian degenerative retinopathy of man, involving death of rod photoreceptors, cone cell degeneration, retinal vessel attenuation and pigmentary deposits. The patient experiences night blindness, usually followed by progressive loss of visual field. Genetic linkage between an autosomal dominant RP locus and rhodopsin, the photoreactive pigment of the rod cells, led to the identification of mutations within the rhodopsin gene in both dominant and recessive forms of RP. To better understand the functional and structural role of rhodopsin in the normal retina and in the pathogenesis of retinal disease, we generated mice carrying a targeted disruption of the rhodopsin gene. Rho-/- mice do not elaborate rod outer segments, losing their photoreceptors over 3 months. There is no rod ERG response in 8-week-old animals. Rho+/- animals retain the majority of their photoreceptors although the inner and outer segments of these cells display some structural disorganization, the outer segments becoming shorter in older mice. These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potential of re-introducing functional rhodopsin genes into degenerating retinal tissues.
视网膜色素变性（RP）是人类最常见的孟德尔遗传性视网膜退行性疾病，涉及视杆光感受器死亡、视锥细胞变性、视网膜血管变细和色素沉着。患者会出现夜盲症，通常随后会逐渐丧失视野。常染色体显性RP位点与视紫红质（视杆细胞的光反应色素）之间的遗传连锁，导致在显性和隐性RP形式中均鉴定出视紫红质基因内的突变。为了更好地理解视紫红质在正常视网膜以及视网膜疾病发病机制中的功能和结构作用，我们培育了携带视紫红质基因靶向缺失的小鼠。Rho-/-小鼠不会形成视杆细胞外节，在3个月内失去其光感受器。8周龄动物没有视杆细胞视网膜电图反应。Rho+/-动物保留了大部分光感受器，尽管这些细胞的内节和外节显示出一些结构紊乱，老年小鼠的外节变短。这些动物应提供一个有用的遗传背景，可在其上表达其他突变视蛋白转基因，以及作为一个模型来评估将功能性视紫红质基因重新引入退化视网膜组织的治疗潜力。
