LaVail M M, White M P, Gorrin G M, Yasumura D, Porrello K V, Mullen R J
Department of Anatomy, University of California, San Francisco 94143-0730.
J Comp Neurol. 1993 Jul 8;333(2):168-81. doi: 10.1002/cne.903330204.
Nervous is an autosomal recessive mutation in mice (gene symbol, nr) that produces a progressive cerebellar and retinal degeneration. We have examined various cytopathological features of the photoreceptor degeneration by light microscopy. An increase in the number of pyknotic photoreceptor nuclei in the outer nuclear layer (ONL) is first seen at postnatal day (P) 11. Between P13 and P19 there is a rapid loss of photoreceptors, with the ONL about 60% the thickness of littermate controls at P19. Between P19 and 2.5 months of age, photoreceptor cell loss is minimal, and there is a relatively slow loss of these cells between 3 and 7.5 months of age. At 7.5 months, the ONL consists of single row of nuclei, most of which are lost over the ensuing months, although a few photoreceptor nuclei persist at 17 months of age and older. Both rods and cones are lost at comparable rates for the first 2 months of life, but rods are somewhat preferentially lost at later ages. A very slight central-to-peripheral gradient of photoreceptor degeneration exists in the nr/nr retina, but no superior-inferior hemispheric differences are evident. The rate, spatiotemporal gradient, and hemispheric similarity in photoreceptor degeneration are the same in albino nr/nr mice reared either in cyclic light or in the dark, and in pigmented nr/nr mice. Autoradiographic analysis of rod outer segment renewal shows that outer segment membranes are synthesized in nervous homozygotes. Rhythmic outer segment disc shedding and phagocytosis by the retinal pigment epithelium occur at approximately normal rates in nr/nr mice. Histochemical and immunocytochemical study of the interphotoreceptor matrix (IPM) reveals the exclusion of stainable IPM from the outer segment zone by lamellar whorls of outer segment membrane, accumulation of stainable IPM in the basal region of the outer segment zone, and the absence of an intense band of stainable IPM at the apical surface of the retinal pigment epithelium. These changes in the IPM are similar to those seen in the Royal College of Surgeons rat. However, comparison of cytopathological changes in these two mutants reveal that the IPM defect probably is not the primary cause of photoreceptor cell death in nr/nr mice, and that similar phenotypic appearance does not necessarily signify similar pathological processes.
Nervous是小鼠中的一种常染色体隐性突变（基因符号为nr），会导致进行性小脑和视网膜退化。我们通过光学显微镜检查了光感受器退化的各种细胞病理学特征。在外核层（ONL）中，固缩的光感受器细胞核数量增加首先在出生后第11天（P11）被观察到。在P13至P19之间，光感受器迅速丧失，在P19时，ONL的厚度约为同窝对照的60%。在P19至2.5月龄之间，光感受器细胞丧失最少，而在3至7.5月龄之间，这些细胞的丧失相对缓慢。在7.5月龄时，ONL由单排细胞核组成，其中大部分在随后的几个月中丧失，尽管在17月龄及更大年龄时仍有一些光感受器细胞核留存。在生命的前2个月中，视杆细胞和视锥细胞以相当的速率丧失，但在后期，视杆细胞的丧失略占优势。在nr/nr视网膜中，存在非常轻微的从中央到周边的光感受器退化梯度，但没有明显的上下半球差异。在循环光照或黑暗环境中饲养的白化nr/nr小鼠以及有色nr/nr小鼠中，光感受器退化的速率、时空梯度和半球相似性是相同的。对视杆细胞外段更新的放射自显影分析表明，外段膜在nervous纯合子中合成。nr/nr小鼠中，视网膜色素上皮细胞的外段盘状结构有节奏地脱落和吞噬以大致正常的速率发生。对视感受器间基质（IPM）的组织化学和免疫细胞化学研究揭示，外段膜的层状螺旋结构将可染色的IPM排除在外段区域，可染色的IPM在外段区域的基部积累，并且在视网膜色素上皮细胞的顶端表面没有可染色IPM的强带。IPM中的这些变化与在皇家外科学院大鼠中观察到的变化相似。然而，对这两种突变体细胞病理学变化的比较表明，IPM缺陷可能不是nr/nr小鼠中光感受器细胞死亡的主要原因，并且相似的表型外观不一定意味着相似的病理过程。
