Lasser Micaela, Pratt Benjamin, Monahan Connor, Kim Seung Woo, Lowery Laura Anne
Department of Biology, Boston College, Chestnut Hill, MA, United States.
Front Physiol. 2019 Jun 26;10:817. doi: 10.3389/fphys.2019.00817. eCollection 2019.
Wolf-Hirschhorn syndrome (WHS) is a rare developmental disorder characterized by intellectual disability and various physical malformations including craniofacial, skeletal, and cardiac defects. These phenotypes, as they involve structures that are derived from the cranial neural crest, suggest that WHS may be associated with abnormalities in neural crest cell (NCC) migration. This syndrome is linked with assorted mutations on the short arm of chromosome 4, most notably the microdeletion of a critical genomic region containing several candidate genes. However, the function of these genes during embryonic development, as well as the cellular and molecular mechanisms underlying the disorder, are still unknown. The model organism offers a number of advantages for studying WHS. With the genome sequenced, genetic manipulation strategies can be readily designed in order to alter the dosage of the WHS candidate genes. Moreover, a variety of assays are available for use in to examine how manipulation of WHS genes leads to changes in the development of tissue and organ systems affected in WHS. In this review article, we highlight the benefits of using as a model system for studying human genetic disorders of development, with a focus on WHS.
沃尔夫-赫希霍恩综合征（WHS）是一种罕见的发育障碍，其特征为智力残疾以及包括颅面、骨骼和心脏缺陷在内的各种身体畸形。这些表型涉及源自颅神经嵴的结构，这表明WHS可能与神经嵴细胞（NCC）迁移异常有关。该综合征与4号染色体短臂上的各种突变有关，最显著的是一个包含几个候选基因的关键基因组区域的微缺失。然而，这些基因在胚胎发育过程中的功能以及该疾病的细胞和分子机制仍然未知。模式生物为研究WHS提供了许多优势。随着其基因组被测序，可以很容易地设计遗传操作策略来改变WHS候选基因的剂量。此外，有多种检测方法可用于研究WHS基因的操作如何导致受WHS影响的组织和器官系统发育的变化。在这篇综述文章中，我们强调了使用该模式生物作为研究人类发育遗传疾病的模型系统的好处，重点是WHS。
