Craniofacial and cardiac defects in chd7 zebrafish mutants mimic CHARGE syndrome.
Craniofacial and cardiac defects in chd7 zebrafish mutants mimic CHARGE syndrome.
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DOI：
10.3389/fcell.2022.1030587
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
近 80% 的 CHARGE 综合征患者患有先天性心脏缺陷，这是一种偶发性疾病，由于 CHD7 基因突变导致颅面和其他异常。已经建立了模拟 CHARGE 综合征的动物模型；然而，在使用吗啉注射或基因突变体的 CHARGE 斑马鱼疾病模型中，心脏缺陷并未得到广泛描述。在这里，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。这些突变表型在母本合子突变背景中得到增强。在chd7突变鱼中，我们发现颅面软骨缩短并形成额外的软骨。此外，chd7 突变体的腹主动脉长度发生改变。许多 CHARGE 患者存在主动脉弓异常。值得注意的是，在 chd7 鱼类突变体中首次观察到第一鳃弓动脉的异常分支。为了了解 CHARGE 综合征的细胞机制，我们使用 sox10:Cre 谱系追踪技术对颅面和心血管组织中的神经嵴细胞 (NCC) 进行了检查。与其在颅内 NCC 中的功能相反，我们发现在 chd7 突变鱼中，沿腹主动脉和主动脉弓的心脏 NCC 衍生壁细胞不受影响。我们生成的chd7鱼突变体概括了在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。
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.
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影响因子：
5.6
作者：
Allen, Mark D.;Religa, Tomasz L.;Bycroft, Mark
通讯作者：
Bycroft, Mark
DOI：
10.1126/science.aba4767
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fabian P;Tseng KC;Smeeton J;Lancman JJ;Dong PDS;Cerny R;Crump JG
通讯作者：
Crump JG
影响因子：
2.7
作者：
Cavanaugh AM;Huang J;Chen JN
通讯作者：
Chen JN
影响因子：
3.5
作者：
Bosman, EA;Penn, AC;Steel, KP
通讯作者：
Steel, KP
影响因子：
3.5
作者：
Asad, Zainab;Pandey, Aditi;Sachidanandan, Chetana
通讯作者：
Sachidanandan, Chetana