Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart.
Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart.
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DOI：
10.3389/fcell.2021.676543
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发表时间：
2021
影响因子：
5.5
通讯作者：
Oakey RJ
中科院分区：
文献类型：
--
作者：
Prickett AR;Montibus B;Barkas N;Amante SM;Franco MM;Cowley M;Puszyk W;Shannon MF;Irving MD;Madon-Simon M;Ward A;Schulz R;Baldwin HS;Oakey RJ
多巴脱羧酶(DDC)在发育中的小鼠心脏中合成5-羟色胺，由DDC_exon1a编码，DDC_exon1a是一种组织特异性父系表达的印迹基因。DDC_exon1a与小鼠11号染色体上母系表达的印记Grb10基因具有相同的印记控制区(ICR)，但对DDC_exon1a的组织特异性印记表达知之甚少。荧光免疫染色将DDC定位于出生前小鼠心脏发育中的心肌，该区域对发育异常敏感，并与人类先天性心脏缺陷有关。DDC_exon1a和Grb10在心脏和脑中没有共表达，Grb10也是父系表达的，尽管它们有相同的ICR，这表明它们通过共同的ICR而不是Grb10基因的表达而机械地联系在一起。来自DDC_exon1a基因敲除小鼠模型的证据表明，它参与了发育中的心肌的生长，并在被检测的少数突变小鼠中观察到心肌变薄，并通过微阵列分析检测到基因表达的变化。在人类心脏发育中的比较研究表明，在DDC_EXON1a处，个体心脏之间存在父系表达偏见和多态印记模式，这一发现与人类其他印记基因一致。
Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human.