Chalmel Frédéric, Léveillard Thierry, Jaillard Céline, Lardenois Aurélie, Berdugo Naomi, Morel Emmanuelle, Koehl Patrice, Lambrou George, Holmgren Arne, Sahel José A, Poch Olivier
Division of Bioinformatics, Swiss Institute of Bioinformatics, University of Basel, CH-4056 Basel, Switzerland.
BMC Mol Biol. 2007 Aug 31;8:74. doi: 10.1186/1471-2199-8-74.
Cone degeneration is the hallmark of the inherited retinal disease retinitis pigmentosa. We have previously identified a trophic factor "Rod-derived Cone Viability Factor (RdCVF) that is secreted by rods and promote cone viability in a mouse model of the disease.
Here we report the bioinformatic identification and the experimental analysis of RdCVF2, a second trophic factor belonging to the Rod-derived Cone Viability Factor family. The mouse RdCVF gene is known to be bifunctional, encoding both a long thioredoxin-like isoform (RdCVF-L) and a short isoform with trophic cone photoreceptor viability activity (RdCVF-S). RdCVF2 shares many similarities with RdCVF in terms of gene structure, expression in a rod-dependent manner and protein 3D structure. Furthermore, like RdCVF, the RdCVF2 short isoform exhibits cone rescue activity that is independent of its putative thiol-oxydoreductase activity.
Taken together, these findings define a new family of bifunctional genes which are: expressed in vertebrate retina, encode trophic cone viability factors, and have major therapeutic potential for human retinal neurodegenerative diseases such as retinitis pigmentosa.
视锥细胞变性是遗传性视网膜疾病视网膜色素变性的标志。我们之前已经鉴定出一种营养因子“视杆细胞衍生的视锥细胞存活因子（RdCVF）”，它由视杆细胞分泌，并在该疾病的小鼠模型中促进视锥细胞的存活。
在此我们报告RdCVF2的生物信息学鉴定和实验分析，RdCVF2是视杆细胞衍生的视锥细胞存活因子家族中的第二个营养因子。已知小鼠RdCVF基因具有双功能，编码一种长的硫氧还蛋白样异构体（RdCVF-L）和一种具有营养性视锥光感受器存活活性的短异构体（RdCVF-S）。在基因结构、以视杆细胞依赖性方式表达以及蛋白质三维结构方面，RdCVF2与RdCVF有许多相似之处。此外，与RdCVF一样，RdCVF2短异构体表现出视锥细胞拯救活性，且与其假定的硫醇氧化还原酶活性无关。
综上所述，这些发现定义了一个新的双功能基因家族，它们：在脊椎动物视网膜中表达，编码营养性视锥细胞存活因子，并且对视网膜色素变性等人类视网膜神经退行性疾病具有重大治疗潜力。
