PDF(Pubmed)
Abstract：
Congenital heart defects occur in almost 80% of patients with CHARGE syndrome, a sporadically occurring disease causing craniofacial and other abnormalities due to mutations in the CHD7 gene. Animal models have been generated to mimic CHARGE syndrome; however, heart defects are not extensively described in zebrafish disease models of CHARGE using morpholino injections or genetic mutants. Here, we describe the co-occurrence of craniofacial abnormalities and heart defects in zebrafish chd7 mutants. These mutant phenotypes are enhanced in the maternal zygotic mutant background. In the chd7 mutant fish, we found shortened craniofacial cartilages and extra cartilage formation. Furthermore, the length of the ventral aorta is altered in chd7 mutants. Many CHARGE patients have aortic arch anomalies. It should be noted that the aberrant branching of the first branchial arch artery is observed for the first time in chd7 fish mutants. To understand the cellular mechanism of CHARGE syndrome, neural crest cells (NCCs), that contribute to craniofacial and cardiovascular tissues, are examined using sox10:Cre lineage tracing. In contrast to its function in cranial NCCs, we found that the cardiac NCC-derived mural cells along the ventral aorta and aortic arch arteries are not affected in chd7 mutant fish. The chd7 fish mutants we generated recapitulate some of the craniofacial and cardiovascular phenotypes found in CHARGE patients and can be used to further determine the roles of CHD7.
摘要：
先天性心脏缺陷发生在几乎80％的CHARGE综合征患者中，一种由于CHD7基因突变而引起颅面和其他异常的偶发疾病。已经产生了模拟CHARGE综合征的动物模型；然而，在斑马鱼CHARGE疾病模型中，使用吗啉代注射或基因突变没有广泛描述心脏缺陷。这里,我们描述了斑马鱼chd7突变体中颅面异常和心脏缺陷的同时发生。这些突变表型在母体合子突变体背景中增强。在chd7突变鱼中，我们发现颅面软骨缩短和额外的软骨形成。此外，在chd7突变体中腹主动脉的长度改变。许多CHARGE患者有主动脉弓异常。应该注意的是，在chd7鱼突变体中首次观察到第一分支弓动脉的异常分支。了解CHARGE综合征的细胞机制,神经c细胞（NCC），有助于颅面和心血管组织，使用sox10：Cre谱系追踪进行检查。与它在颅骨NCC中的功能相反，我们发现，在chd7突变鱼中，沿着腹主动脉和主动脉弓动脉的心脏NCC衍生壁细胞不受影响。我们生成的chd7鱼突变体概括了CHARGE患者中发现的一些颅面和心血管表型，可用于进一步确定CHD7的作用。
