Developmental Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Mamm Genome. 2011 Aug;22(7-8):362-76. doi: 10.1007/s00335-011-9335-5. Epub 2011 Jun 11.
The defining characteristic of all vertebrates is a spine composed of a regular sequence of vertebrae. In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1,000 live births and arise when the formation of vertebral precursors in the embryo is disrupted. These precursors (somites) form in a process (somitogenesis) in which each somite is progressively separated from an unsegmented precursor tissue. In the past decade the underlying genetic mechanisms driving this complex process have been dissected using animal models, revealing that it requires the coordinated action of at least 300 genes. Deletion of many of these genes in the mouse produces phenotypes with similar vertebral defects to those observed in human congenital abnormalities. This review highlights the role that such mouse models have played in the identification of the genetic causes of the malsegmentation syndrome spondylocostal dysostosis.
所有脊椎动物的特征是由一系列规则排列的脊椎组成的脊柱。在人类中，先天性脊柱缺陷的发病率为每 1000 例活产儿中有 0.5-1 例，当胚胎中脊椎前体的形成受到干扰时就会发生这种缺陷。这些前体（体节）在一个过程（体节发生）中形成，其中每个体节逐渐从未分段的前体组织中分离出来。在过去的十年中，使用动物模型对驱动这一复杂过程的潜在遗传机制进行了剖析，揭示了它至少需要 300 个基因的协调作用。在小鼠中删除许多这样的基因会产生与在人类先天性异常中观察到的类似的脊椎缺陷表型。这篇综述强调了这些小鼠模型在确定多发性骨发育不良综合征脊柱肋发育不良的遗传原因方面所发挥的作用。
