A previous study suggested that human Coffin-Siris syndrome is related to the mutation of SOX11. Since the homozygous SOX11 mutant mice died soon after birth, no suitable model was available for the study of the pathogenic mechanism of Coffin-Siris syndrome. To solve this problem, we generated two viable homozygous zebrafish mutants, sox11a^m/m and sox11b^m/m. We found that the sox11a^m/m mutant possessed Coffin-Siris syndrome features. The sox11a^m/m mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the sox11a^m/m mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of sox11a mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the sox11a^m/m mutant, indicating that sox11a mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that sox11a^m/m mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.

中文翻译：

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具有 Coffin-Siris 综合征特征的 sox11a 突变斑马鱼的多重发育缺陷

先前的一项研究表明，人类 Coffin-Siris 综合征与SOX11的突变有关。由于纯合SOX11突变小鼠出生后不久即死亡，因此尚无合适的模型可用于研究Coffin-Siris综合征的发病机制。为了解决这个问题，我们生成了两个可行的纯合斑马鱼突变体，sox11a ^m/m和sox11b ^m/m。我们发现sox11a ^m/m突变体具有 Coffin-Siris 综合征的特征。sox11a ^m/m突变体表现出从 3.3 hpf 胚胎到成年期的生长缺陷。此外，sox11a ^m/m突变体在成人中还表现出小头畸形、瞳孔缩小、软骨发育不全和骨骼畸形。在单细胞阶段注射sox11a mRNA可以挽救生长缺陷。此外，sox11a ^m/m突变体中软骨和骨骼相关基因的表达水平下调，表明sox11a主要通过调节骨骼发育相关基因的表达来影响斑马鱼的生长发育。我们的研究结果表明，sox11a ^m/m突变斑马鱼提供了一个潜在的模型系统，以帮助寻找人类 Coffin-Siris 综合征的致病机制。