Congenital heart defects are a feature of several genetic haploinsufficiency syndromes, often involving transcriptional regulators. One property of haploinsufficient genes is their propensity for network interactions at the gene or protein level. In this article we took advantage of an online dataset of high throughput screening of mutations that are embryonic lethal in mice. Our aim was to identify new genes where the loss of function caused cardiovascular phenotypes resembling the 22q11.2 deletion syndrome models, that is, heterozygous and homozygous loss of Tbx1. One gene with a potentially haploinsufficient phenotype was identified, Setd5, thought to be involved in chromatin modification. We found murine Setd5 haploinsufficiency to be associated with double outlet right ventricle and perimembranous ventricular septal defect, although no genetic interaction with Tbx1 was detected. Conditional mutagenesis revealed that Setd5 was required in cardiopharyngeal mesoderm for progression of the heart tube through the ballooning stage to create a four-chambered heart.

中文翻译：

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Setd5 是心咽中胚层心脏发育所必需的，其单倍体不足与小鼠流出道缺陷有关

先天性心脏缺陷是几种遗传单倍体不足综合征的特征，通常涉及转录调节因子。单倍体不足基因的一个特性是它们倾向于在基因或蛋白质水平上进行网络相互作用。在本文中，我们利用了对小鼠胚胎致死突变进行高通量筛选的在线数据集。我们的目的是鉴定新基因，其中功能丧失导致类似于 22q11.2 缺失综合征模型的心血管表型，即Tbx1的杂合子和纯合子丢失。鉴定了一个具有潜在单倍体不足表型的基因Setd5，被认为与染色质修饰有关。我们找到了鼠Setd5单倍体不足与双出口右心室和膜周室间隔缺损相关，尽管未检测到与Tbx1的遗传相互作用。条件诱变显示，心咽中胚层需要Setd5才能使心管通过气球阶段进展以形成四腔心脏。