Shorbaji Ayat, Pushparaj Peter Natesan, Bakhashab Sherin, Al-Ghafari Ayat B, Al-Rasheed Rana R, Siraj Mira Loubna, Basabrain Mohammad Abdullah, Alsulami Majed, Abu Zeid Isam M, Naseer Muhammad Imran, Rasool Mahmood
Biochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia.
Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Bioinformation. 2024 May 31;20(5):415-429. doi: 10.6026/973206300200415. eCollection 2024.
Congenital heart disease (CHD) encompasses a diverse range of structural and functional anomalies that affect the heart and the major blood vessels. Epidemiological studies have documented a global increase in CHD prevalence, which can be attributed to advancements in diagnostic technologies. Extensive research has identified a plethora of CHD-related genes, providing insights into the biochemical pathways and molecular mechanisms underlying this pathological state. In this review, we discuss the advantages and challenges of various and CHD models, including primates, canines, Xenopus frogs, rabbits, chicks, mice, Drosophila, zebrafish, and induced pluripotent stem cells (iPSCs). Primates are closely related to humans but are rare and expensive. Canine models are costly but structurally comparable to humans. Xenopus frogs are advantageous because of their generation of many embryos, ease of genetic modification, and cardiac similarity. Rabbits mimic human physiology but are challenging to genetically control. Chicks are inexpensive and simple to handle; however, cardiac events can vary among humans. Mice differ physiologically, while being evolutionarily close and well-resourced. Drosophila has genes similar to those of humans but different heart structures. Zebrafish have several advantages, including high gene conservation in humans and physiological cardiac similarities but limitations in cross-reactivity with mammalian antibodies, gene duplication, and limited embryonic stem cells for reverse genetic methods. iPSCs have the potential for gene editing, but face challenges in terms of 2D structure and genomic stability. CRISPR-Cas9 allows for genetic correction but requires high technical skills and resources. These models have provided valuable knowledge regarding cardiac development, disease simulation, and the verification of genetic factors. This review highlights the distinct features of various models with respect to their biological characteristics, vulnerability to developing specific heart diseases, approaches employed to induce particular conditions, and the comparability of these species to humans. Therefore, the selection of appropriate models is based on research objectives, ultimately leading to an enhanced comprehension of disease pathology and therapy.
先天性心脏病（CHD）涵盖了一系列影响心脏和主要血管的结构和功能异常。流行病学研究表明，全球先天性心脏病的患病率呈上升趋势，这可归因于诊断技术的进步。广泛的研究已经确定了大量与先天性心脏病相关的基因，为深入了解这种病理状态背后的生化途径和分子机制提供了线索。在本综述中，我们讨论了各种先天性心脏病模型的优缺点，包括灵长类动物、犬类、非洲爪蟾、兔子、小鸡、小鼠、果蝇、斑马鱼和诱导多能干细胞（iPSC）。灵长类动物与人类关系密切，但数量稀少且价格昂贵。犬类模型成本高昂，但结构与人类相似。非洲爪蟾具有优势，因为它们能产生许多胚胎，易于进行基因改造，且心脏结构相似。兔子模拟人类生理机能，但在基因控制方面具有挑战性。小鸡价格便宜且易于操作；然而，人类之间的心脏事件可能存在差异。小鼠在生理上有所不同，但其在进化上与人类接近且资源丰富。果蝇具有与人类相似的基因，但心脏结构不同。斑马鱼有几个优点，包括与人类基因高度保守以及生理心脏相似，但在与哺乳动物抗体的交叉反应、基因复制以及用于反向遗传方法的胚胎干细胞有限等方面存在局限性。诱导多能干细胞具有基因编辑的潜力，但在二维结构和基因组稳定性方面面临挑战。CRISPR-Cas9可进行基因校正，但需要高技术技能和资源。这些模型为心脏发育、疾病模拟和遗传因素验证提供了有价值的知识。本综述强调了各种模型在生物学特征、患特定心脏病的易感性、诱导特定条件所采用的方法以及这些物种与人类的可比性方面的独特特征。因此，选择合适的模型应基于研究目标，最终有助于增强对疾病病理学和治疗方法的理解。
