Fragile X syndrome (FXS) is the most common inheritable form of intellectual disability. FMR1, the gene responsible for FXS, is located on human chromosome Xq27.3 and contains a stretch of CGG trinucleotide repeats in its 5′ untranslated region. FXS is caused by CGG repeats that expand beyond 200, resulting in FMR1 silencing via promoter hypermethylation. The molecular mechanism underlying CGG repeat expansion, a fundamental cause of FXS, remains poorly understood, partly due to a lack of experimental systems. Accumulated evidence indicates that the large chromosomal region flanking a CGG repeat is critical for repeat dynamics. In the present study, we isolated and introduced whole human X chromosomes from healthy, FXS premutation carriers, or FXS patients who carried disease condition-associated CGG repeat lengths, into mouse A9 cells via microcell-mediated chromosome transfer. The CGG repeat length-associated methylation status and human FMR1 expression in these monochromosomal hybrid cells mimicked those in humans. Thus, this set of A9 cells containing CGG repeats from three different origins (FXS-A9 panel) may provide a valuable resource for investigating a series of genetic and epigenetic CGG repeat dynamics during FXS pathogenesis.

脆弱X综合征（FXS）是智力障碍的最常见可遗传形式。负责FXS的基因FMR1位于人类染色体Xq27.3上，并在其5'非翻译区包含一段CGG三核苷酸重复序列。FXS是由CGG重复次数超过200而导致的，从而导致FMR1通过启动子高甲基化沉默。CGG重复扩增是FXS的根本原因，其分子机制仍知之甚少，部分原因是缺乏实验系统。积累的证据表明，CGG重复序列侧翼的大染色体区域对于重复动力学至关重要。在本研究中，我们从健康，FXS预突变携带者或携带疾病状况相关CGG重复长度的FXS患者中，通过微细胞介导的染色体转移将整个人类X染色体分离并引入到小鼠A9细胞中。CGG重复长度相关的甲基化状态和人类FMR1这些单核杂交细胞中的表达与人类相似。因此，这组包含来自三个不同来源的CGG重复序列的A9细胞（FXS-A9面板）可为研究FXS发病机理中一系列遗传和表观遗传CGG重复动力学提供有价值的资源。