Quelle-Regaldie Ana, Folgueira Mónica, Yáñez Julián, Sobrido-Cameán Daniel, Alba-González Anabel, Barreiro-Iglesias Antón, Sobrido María-Jesús, Sánchez Laura
Department of Zoology, Genetics and Physical Anthropology, Faculty of Veterinary Science, University of Santiago de Compostela, 27002 Lugo, Spain.
Instituto de Investigación Biomédica de A Coruña (INIBIC), Servicio Galego de Saúde, 15008 La Coruña, Spain.
Biomedicines. 2022 Jul 28;10(8):1814. doi: 10.3390/biomedicines10081814.
NOP56 belongs to a C/D box small nucleolar ribonucleoprotein complex that is in charge of cleavage and modification of precursor ribosomal RNAs and assembly of the 60S ribosomal subunit. An intronic expansion in gene causes Spinocerebellar Ataxia type 36, a typical late-onset autosomal dominant ataxia. Although vertebrate animal models were created for the intronic expansion, none was studied for the loss of function of . We studied a zebrafish loss-of-function model of the gene which shows 70% homology with the human gene. We observed a severe neurodegenerative phenotype in mutants, characterized mainly by absence of cerebellum, reduced numbers of spinal cord neurons, high levels of apoptosis in the central nervous system (CNS) and impaired movement, resulting in death before 7 days post-fertilization. Gene expression of genes related to C/D box complex, balance and CNS development was impaired in mutants. In our study, we characterized the first NOP56 loss-of-function vertebrate model, which is important to further understand the role of NOP56 in CNS function and development.
NOP56属于一种C/D盒小核仁核糖核蛋白复合体，负责前体核糖体RNA的切割和修饰以及60S核糖体亚基的组装。该基因中的内含子扩增会导致36型脊髓小脑共济失调，这是一种典型的晚发性常染色体显性共济失调。尽管针对内含子扩增构建了脊椎动物动物模型，但尚未对该基因功能丧失进行研究。我们研究了与人类基因具有70%同源性的该基因的斑马鱼功能丧失模型。我们在该基因突变体中观察到严重的神经退行性表型，主要特征为小脑缺失、脊髓神经元数量减少、中枢神经系统（CNS）中高水平的细胞凋亡以及运动受损，导致在受精后7天内死亡。该基因突变体中与C/D盒复合体、平衡和中枢神经系统发育相关基因的表达受损。在我们的研究中，我们鉴定了首个NOP56功能丧失的脊椎动物模型，这对于进一步了解NOP56在中枢神经系统功能和发育中的作用具有重要意义。
