Department of Developmental Medicine, Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi, Osaka, Japan.
Dev Growth Differ. 2012 Jun;54(5):588-604. doi: 10.1111/j.1440-169X.2012.01362.x.
Roberts syndrome and SC phocomelia (RBS/SC) are genetic autosomal recessive syndromes caused by establishment of cohesion 1 homolog 2 ( ESCO 2) mutation. RBS/SC appear to have a variety of clinical features, even with the same mutation of the ESCO2 gene. Here, we established and genetically characterized a medaka model of RBS/SC by reverse genetics. The RBS/SC model was screened from a mutant medaka library produced by the Targeting Induced Local Lesions in Genomes method. The medaka mutant carrying the homozygous mutation at R80S in the conserved region of ESCO2 exhibited clinical variety (i.e. developmental arrest with craniofacial and chromosomal abnormalities and embryonic lethality) as characterized in RBS/SC. Moreover, widespread apoptosis and downregulation of some gene expression, including notch1a, were detected in the R80S mutant. The R80S mutant is the animal model for RBS/SC and a valuable resource that provides the opportunity to extend knowledge of ESCO2. Downregulation of some gene expression in the R80S mutant is an important clue explaining non-correlation between genotype and phenotype in RBS/SC.
罗伯茨综合征伴海豹肢畸形（RBS/SC）是由着丝粒凝聚蛋白 1 同源物 2（ESCO2）突变引起的常染色体隐性遗传综合征。RBS/SC 表现出多种临床特征，即使 ESCO2 基因突变相同。在这里，我们通过反向遗传学建立并遗传表征了 RBS/SC 的斑马鱼模型。该 RBS/SC 模型是从通过靶向基因组局部诱导突变（Targeting Induced Local Lesions in Genomes，TILLING）方法产生的突变斑马鱼文库中筛选出来的。携带 ESCO2 保守区域 R80S 纯合突变的斑马鱼突变体表现出 RBS/SC 特征的临床多样性（即发育停滞伴颅面和染色体异常以及胚胎致死）。此外，在 R80S 突变体中检测到广泛的细胞凋亡和一些基因表达（包括 notch1a）下调。R80S 突变体是 RBS/SC 的动物模型，也是一个有价值的资源，为扩展对 ESCO2 的认识提供了机会。R80S 突变体中一些基因表达的下调是解释 RBS/SC 中基因型与表型不相关的重要线索。
