Goergen Craig J, Li Hong-Hua, Francke Uta, Taylor Charles A
Department of Bioengineering, Stanford University School of Medicine, Stanford, Calif., USA.
J Vasc Res. 2011;48(2):119-29. doi: 10.1159/000316808. Epub 2010 Oct 7.
The Williams-Beuren syndrome (WBS) is a genetic disorder caused by a heterozygous ~1.5-Mb deletion. The aim of this study was to determine how the genetic changes in a Wbs mouse model alter Eln expression, blood pressure, vessel structure, and abdominal aortic wall dynamics in vivo.
Elastin (ELN) transcript levels were quantified by qRT-PCR and blood pressure was measured with a tail cuff system. M-mode ultrasound was used to track pulsatile abdominal aortic wall motion. Aortas were sectioned and stained to determine medial lamellar structure.
ELN transcript levels were reduced by 38-41% in Wbs mice lacking one copy of the ELN gene. These mice also had a 10-20% increase in mean blood pressure and significantly reduced circumferential cyclic strain (p < 0.001). Finally, histological sections showed disorganized and fragmented elastin sheets in Wbs mice, but not the characteristic increase in lamellar units seen in Eln(+/-) mice.
The deletion of Eln in this Wbs mouse model results in lower gene expression, hypertension, reduced cyclic strain, and fragmented elastin sheets. The observation that the number of medial lamellar units is normal in Wbs deletion mice, which is in contrast to Eln(+/-) mice, suggests other genes may be involved in vascular development.
威廉姆斯-贝伦综合征（WBS）是一种由杂合性约1.5兆碱基缺失引起的遗传性疾病。本研究的目的是确定Wbs小鼠模型中的基因变化如何在体内改变Eln表达、血压、血管结构和腹主动脉壁动力学。
通过qRT-PCR定量弹性蛋白（ELN）转录水平，并用尾套系统测量血压。使用M型超声跟踪腹主动脉壁的搏动运动。将主动脉切片并染色以确定中膜层状结构。
在缺失一个ELN基因拷贝的Wbs小鼠中，ELN转录水平降低了38%-41%。这些小鼠的平均血压也升高了10%-20%，圆周循环应变显著降低（p<0.001）。最后，组织学切片显示Wbs小鼠的弹性蛋白片紊乱且破碎，但未出现Eln(+/-)小鼠中特征性的层状单元增加。
该Wbs小鼠模型中Eln的缺失导致基因表达降低、高血压、循环应变降低和弹性蛋白片破碎。与Eln(+/-)小鼠相反，Wbs缺失小鼠中膜层状单元数量正常，这一观察结果表明其他基因可能参与血管发育。
