Keiser Nicholas W, Tang Waixing, Wei Zhangyong, Bennett Jean
Department of Ophthalmology, F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104-6069, USA.
Mol Vis. 2005 Dec 7;11:1052-60.
Choroideremia (CHM), an X-linked retinal disease, is caused by mutations affecting the CHM gene. This gene encodes REP-1, which functions in the covalent modifications of proteins involved in vesicle trafficking. The disease affects several cell types in the retina, but it is not known which cell types contribute directly or indirectly to disease progression. A study of the expression patterns of Chm and the related gene Chml in the mouse retina was undertaken in order to address this issue.
The expression patterns of Chm and Chml were determined by in situ hybridization. The localization of the Chm protein product, Rep-1, was determined spatially and temporally in the mouse retina by immunohistochemistry.
Chm and Chml mRNA were found in every major layer of the retina in adult mice. During development, Rep-1 protein localization changes from a fairly diffuse pattern during embryogenesis to a more specific pattern at the time of retinal differentiation. In adulthood, Rep-1 localizes to distinct cellular compartments in multiple retinal cell types.
Chm and Chml have the same broad expression profile in the mouse retina. In particular, the Chm transcript and corresponding protein are found in cell types other than those thought to be primarily affected in the human disease. These results have important implications for approaches with which to develop a relevant mouse model of choroideremia and for therapeutic strategies for this disease.
视网膜色素变性（CHM）是一种X连锁视网膜疾病，由影响CHM基因的突变引起。该基因编码REP-1，其在参与囊泡运输的蛋白质的共价修饰中发挥作用。该疾病影响视网膜中的多种细胞类型，但尚不清楚哪些细胞类型直接或间接导致疾病进展。为了解决这个问题，对小鼠视网膜中Chm和相关基因Chml的表达模式进行了研究。
通过原位杂交确定Chm和Chml的表达模式。通过免疫组织化学在空间和时间上确定Chm蛋白产物Rep-1在小鼠视网膜中的定位。
在成年小鼠视网膜的每个主要层中都发现了Chm和Chml mRNA。在发育过程中，Rep-1蛋白定位从胚胎发生期间相当分散的模式转变为视网膜分化时更特异的模式。在成年期，Rep-1定位于多种视网膜细胞类型中的不同细胞区室。
Chm和Chml在小鼠视网膜中具有相同的广泛表达谱。特别是，在被认为是人类疾病主要受影响的细胞类型以外的其他细胞类型中发现了Chm转录本和相应的蛋白质。这些结果对于开发相关的视网膜色素变性小鼠模型的方法以及该疾病的治疗策略具有重要意义。
