Induced Chromosome Deletion in a Williams-Beuren Syndrome Mouse Model Causes Cardiovascular Abnormalities

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Abstract
Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

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