International Journal of Molecular Zoology 2024, Vol.14, No.1, 18-21 http://animalscipublisher.com/index.php/ijmz 18 Scientific Review Open Access From Gene to Function: Exploring the Effects of ACTA2 Gene Variants on Cardiac Development YepingHan Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, China Corresponding author email: liviayphan@gmail.com International Journal of Molecular Zoology, 2024, Vol.14, No.1 doi: 10.5376/ijmz.2024.14.0003 Received: 06 Feb., 2024 Accepted: 12 Feb., 2024 Published: 19 Feb., 2024 Copyright © 2024 Han, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Han Y.P., 2024, From gene to function: exploring the effects of ACTA2 gene variants on cardiac development, International Journal of Molecular Zoology, 14(1): 18-21 (doi: 10.5376/ijmz.2024.14.0003) The journal Nature published a paper titled “Cardiac Manifestations of Human ACTA2 Variants Recapitated in a Zebrafish Model” on February 5, 2024, authored by Wulan Apridita Sebastian, Masanori Inoue, Nobuyuki Shimizu and others, from the Department of Cell Biology, Oita University, Faculty of Medicine, Oita, Japan. This study explored the cardiac performance caused by human ACTA2 gene mutations by using a zebrafish model, revealing the effects of ACTA2 G148R and R179H mutations on left ventricular non compression and abnormal cardiac morphology development. The ACTA2 gene encodes vascular smooth muscle cells α-actin β2. It is the main protein in vascular smooth muscle. The missense mutation of ACTA2 gene may lead to hereditary thoracic aortic disease. This study reported a patient with an abnormal mutation in the ACTA2 gene Gly148Arg (G148R), exhibiting rare left ventricular non compression. The pathogenicity of this rare variant in cardiac development and function was validated through live zebrafish models. 1 Experimental Data Analysis The key findings of this study include: zebrafish carrying harmful mutations have significantly reduced heart shortening scores, thinner myocardial walls than wild-type, and significantly reduced total number of cells in the myocardium. These results demonstrate that the ACTA2 G148R and R179H variants have an impact on the development of left ventricular non compression and cardiac morphological abnormalities, emphasizing the unknown importance of the ACTA2 gene in multiple aspects of cardiovascular development. Figure 1 shows the cardiac ultrasound image and MRCP of a patient carrying the ACTA2 G148R variant. Part A shows the long axis view (diastole) of the left ventricle in echocardiography. The ventricular wall of the left ventricle is composed of an outer dense layer (C) and an inner non dense trabecular layer (NC), with a ratio of 2.0 between NC and C. The deep depression formed by the trabecular layer has blood infiltration (indicated by the white arrow). The MRCP in section B shows that the main pancreatic duct in the head area of the pancreas presents a reverse Z-shape (indicated by a black arrow). The chest magnetic resonance imaging of parts C and D showed a shift in the descending part of the aorta. In these imaging findings, it can be noted that the atypical trabecular layer of the left ventricle may be associated with mutations in the ACTA2 gene, while the abnormal orientation of the pancreatic duct and the abnormal appearance of the aorta may also be related to the phenotype of this genetic variation. These findings contribute to understanding how the ACTA2 G148R variant affects the anatomical structure of cardiovascular and pancreatic systems. Figure 2 shows the expression of endogenous ACTA2 in the cardiac region of transgenic zebrafish larvae (labeled as Tg[cmlc2:EGFP]) at 4 days after fertilization. Part A shows the brain region and ACTA2 was not detected, while part B shows a high expression of endogenous ACTA2 in the heart region, with EGFP green fluorescence, red signal stained with anti ACTA2 antibodies, and blue signal stained with DAPI in the nucleus. The high magnification in the image shows a detailed image of immunostaining, with a lack of red signal in the brain, indicating that ACTA2is not expressed or the expression level is extremely low in this region; The overlapping red
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