Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland and Labrador, St. John's, NL A1B 3V6, Canada.
Int J Mol Sci. 2021 Sep 16;22(18):10001. doi: 10.3390/ijms221810001.
Axenfeld-Rieger syndrome (ARS) encompasses a group of developmental disorders that affect the anterior segment of the eye, as well as systemic developmental defects in some patients. Malformation of the ocular anterior segment often leads to secondary glaucoma, while some patients also present with cardiovascular malformations, craniofacial and dental abnormalities and additional periumbilical skin. Genes that encode two transcription factors, and , account for almost half of known cases, while the genetic lesions in the remaining cases remain unresolved. Given the genetic similarity between zebrafish and humans, as well as robust antisense inhibition and gene editing technologies available for use in these animals, loss of function zebrafish models for ARS have been created and shed light on the mechanism(s) whereby mutations in these two transcription factors cause such a wide array of developmental phenotypes. This review summarizes the published phenotypes in zebrafish and loss of function models and discusses possible mechanisms that may be used to target pharmaceutical development and therapeutic interventions.
Axenfeld-Rieger 综合征（ARS）包括一组影响眼睛前段的发育障碍，以及一些患者的全身发育缺陷。眼前段的畸形常导致继发性青光眼，而一些患者还存在心血管畸形、颅面和牙齿异常以及脐周额外皮肤。编码两种转录因子 和 的基因占已知病例的近一半，而其余病例的遗传病变仍未解决。鉴于斑马鱼和人类之间的遗传相似性，以及这些动物中可用的强大反义抑制和基因编辑技术，已经创建了 ARS 的功能丧失斑马鱼模型，并阐明了这两种转录因子中的突变导致如此广泛的发育表型的机制。这篇综述总结了发表的斑马鱼 和 功能丧失模型中的表型，并讨论了可能用于靶向药物开发和治疗干预的可能机制。
