Rodríguez-Martín Mario, Báez-Flores Juan, Ribes Vanessa, Isidoro-García María, Lacal Jesus, Prieto-Matos Pablo
Laboratory of Functional Genetics of Rare Diseases, Department of Microbiology and Genetics, University of Salamanca, 37007 Salamanca, Spain.
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.
Biomedicines. 2024 Apr 10;12(4):841. doi: 10.3390/biomedicines12040841.
RASopathies, a group of neurodevelopmental congenital disorders stemming from mutations in the RAS/MAPK pathway, present a unique opportunity to delve into the intricacies of complex neurological disorders. Afflicting approximately one in a thousand newborns, RASopathies manifest as abnormalities across multiple organ systems, with a pronounced impact on the central and peripheral nervous system. In the pursuit of understanding RASopathies' neurobiology and establishing phenotype-genotype relationships, in vivo non-mammalian models have emerged as indispensable tools. Species such as , , , species and embryos have proven to be invaluable in shedding light on the intricate pathways implicated in RASopathies. Despite some inherent weaknesses, these genetic models offer distinct advantages over traditional rodent models, providing a holistic perspective on complex genetics, multi-organ involvement, and the interplay among various pathway components, offering insights into the pathophysiological aspects of mutations-driven symptoms. This review underscores the value of investigating the genetic basis of RASopathies for unraveling the underlying mechanisms contributing to broader neurological complexities. It also emphasizes the pivotal role of non-mammalian models in serving as a crucial preliminary step for the development of innovative therapeutic strategies.
RAS病是一组源于RAS/丝裂原活化蛋白激酶（MAPK）信号通路突变的神经发育先天性疾病，为深入研究复杂神经系统疾病的复杂性提供了独特契机。RAS病影响约千分之一的新生儿，表现为多个器官系统的异常，对中枢和外周神经系统有显著影响。在致力于理解RAS病的神经生物学并建立表型-基因型关系的过程中，体内非哺乳动物模型已成为不可或缺的工具。诸如[具体物种1]、[具体物种2]、[具体物种3]物种和[具体物种4]胚胎等已被证明在揭示RAS病所涉及的复杂信号通路方面具有极高价值。尽管存在一些固有弱点，但这些遗传模型相对于传统啮齿动物模型具有明显优势，能从整体上展现复杂遗传学、多器官受累情况以及各种信号通路成分之间的相互作用，为深入了解突变驱动症状的病理生理学方面提供见解。本综述强调了研究RAS病遗传基础对于揭示导致更广泛神经复杂性的潜在机制的价值。它还强调了非哺乳动物模型作为创新治疗策略开发关键初步步骤的关键作用。
