PDF(Pubmed)
Abstract：
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 In vitro and in vivo 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.
摘要：
先天性心脏病（CHD）包括影响心脏和主要血管的各种结构和功能异常。流行病学研究表明，冠心病患病率在全球范围内有所增加，这可以归因于诊断技术的进步。广泛的研究已经确定了大量的CHD相关基因，提供对这种病理状态的生化途径和分子机制的见解。在这次审查中,我们讨论了各种体外和体内CHD模型的优势和挑战，包括灵长类动物,犬科动物,非洲爪蛙,兔子,小鸡,老鼠,果蝇,斑马鱼,和诱导多能干细胞（iPSC）。灵长类动物与人类密切相关，但罕见且昂贵。犬类模型成本高，但在结构上与人类相当。非洲爪蛙是有利的，因为它们产生了许多胚胎，易于进行基因改造，心脏相似性兔子模仿人类生理学，但对基因控制具有挑战性。小鸡价格低廉，操作简单；然而，心脏事件可能因人而异。小鼠在生理上不同，同时在进化上接近和资源充足。果蝇的基因与人类相似，但心脏结构不同。斑马鱼有几个优点，包括人类的高基因保守性和生理心脏相似性，但与哺乳动物抗体的交叉反应性有限，基因复制，和用于反向遗传方法的有限胚胎干细胞。iPSCs具有基因编辑的潜力，但在2D结构和基因组稳定性方面面临挑战。CRISPR-Cas9允许基因校正，但需要很高的技术技能和资源。这些模型提供了有关心脏发育的宝贵知识，疾病模拟,和遗传因素的验证。这篇综述强调了各种模型在生物学特征方面的不同特征，容易患上特定的心脏病，用于诱发特定条件的方法，以及这些物种与人类的可比性。因此,选择合适的模型是基于研究目标，最终导致对疾病病理和治疗的理解增强。
