Krebs Luke T, Bradley Cara K, Norton Christine R, Xu Jingxia, Oram Kathleen F, Starling Christa, Deftos Michael L, Bevan Michael J, Gridley Thomas
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
Genesis. 2012 Apr;50(4):366-74. doi: 10.1002/dvg.20813. Epub 2012 Jan 5.
The Notch-regulated ankyrin repeat protein (Nrarp) is a component of a negative feedback system that attenuates Notch pathway-mediated signaling. In vertebrates, the timing and spacing of formation of the mesodermal somites are controlled by a molecular oscillator termed the segmentation clock. Somites are also patterned along the rostral-caudal axis of the embryo. Here, we demonstrate that Nrarp-deficient embryos and mice exhibit genetic background-dependent defects of the axial skeleton. While progression of the segmentation clock occurred in Nrarp-deficient embryos, they exhibited altered rostrocaudal patterning of the somites. In Nrarp mutant embryos, the posterior somite compartment was expanded. These studies confirm an anticipated, but previously undocumented role for the Nrarp gene in vertebrate somite patterning and provide an example of the strong influence that genetic background plays on the phenotypes exhibited by mutant mice.
Notch调节的锚蛋白重复蛋白（Nrarp）是一个负反馈系统的组成部分，该系统可减弱Notch通路介导的信号传导。在脊椎动物中，中胚层体节形成的时间和间距由一个称为分割时钟的分子振荡器控制。体节也沿着胚胎的头-尾轴形成模式。在这里，我们证明Nrarp缺陷型胚胎和小鼠表现出与遗传背景相关的轴向骨骼缺陷。虽然分割时钟在Nrarp缺陷型胚胎中仍在进行，但它们的体节头-尾模式发生了改变。在Nrarp突变体胚胎中，后体节区扩大。这些研究证实了Nrarp基因在脊椎动物体节模式形成中预期但先前未记录的作用，并提供了一个遗传背景对突变小鼠所表现出的表型有强烈影响的例子。
