Wang Hongjie, He Jingwei, Han Xuemei, Wu Xiuzhi, Ye Xuebin, Lv Wenchao, Zu Yao
International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China.
Biology (Basel). 2023 Jun 23;12(7):899. doi: 10.3390/biology12070899.
Mutations in can lead to diseases such as Bosley-Salih-Alorainy syndrome, involving severe cardiovascular malformations. However, the role of in cardiac morphogenesis remains unclear. is a homologous gene to human in zebrafish. We used CRISPR to make -null zebrafish that exhibited multiple heart malformations. In situ hybridization and sections revealed the morphological changes in mutants: enlarged ventricle with thickened myocardium and increased trabeculae, intensified OFT and inadequate heart looping, with electrocardiography supporting these pathological changes. High-speed photography captured cardiac pumping and revealed a significant decrease in cardiac output. Furthermore, lacking led to posterior body abnormality that affected movement ability, corresponding with the motor development delay in patients. Upregulation of paralogues in -null fish implied a compensatory mechanism between genes. Accordingly, we successfully constructed a -null model with a cardiac disease pattern which occurred in human -associated heart malformation. The study of in zebrafish can further promote the understanding of genes and related diseases.
[基因名称]的突变可导致诸如博斯利 - 萨利赫 - 阿洛拉尼综合征等疾病，这些疾病涉及严重的心血管畸形。然而，[基因名称]在心脏形态发生中的作用仍不清楚。[基因名称]是斑马鱼中与人类[基因名称]同源的基因。我们使用CRISPR技术构建了[基因名称]缺失的斑马鱼，这些斑马鱼表现出多种心脏畸形。原位杂交和切片显示了突变体的形态变化：心室扩大，心肌增厚，小梁增多，流出道强化且心脏环化不足，心电图结果支持这些病理变化。高速摄影记录了心脏泵血情况，显示心输出量显著下降。此外，[基因名称]缺失导致鱼体后部异常，影响运动能力，这与相关患者的运动发育迟缓相对应。[基因名称]缺失的鱼中[旁系同源基因名称]的上调暗示了[基因名称]家族基因之间的补偿机制。因此，我们成功构建了一个具有与人类[基因名称]相关心脏畸形中出现的心脏病模式的[基因名称]缺失模型。对斑马鱼中[基因名称]的研究可以进一步促进对[基因名称]家族基因及相关疾病的理解。
