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Research Article Free access | 10.1172/JCI4487

Novel arterial pathology in mice and humans hemizygous for elastin.

D Y Li, G Faury, D G Taylor, E C Davis, W A Boyle, R P Mecham, P Stenzel, B Boak, and M T Keating

Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Cardiology Division and Program in Human Molecular Biology and Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah 84112-5330, USA. dean@howard.genetics.utah.edu

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Published November 15, 1998 - More info

Published in Volume 102, Issue 10 on November 15, 1998
J Clin Invest. 1998;102(10):1783–1787. https://doi.org/10.1172/JCI4487.
© 1998 The American Society for Clinical Investigation
Published November 15, 1998 - Version history
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Abstract

Obstructive vascular disease is an important health problem in the industrialized world. Through a series of molecular genetic studies, we demonstrated that loss-of-function mutations in one elastin allele cause an inherited obstructive arterial disease, supravalvular aortic stenosis (SVAS). To define the mechanism of elastin's effect, we generated mice hemizygous for the elastin gene (ELN +/-). Although ELN mRNA and protein were reduced by 50% in ELN +/- mice, arterial compliance at physiologic pressures was nearly normal. This discrepancy was explained by a paradoxical increase of 35% in the number of elastic lamellae and smooth muscle in ELN +/- arteries. Examination of humans with ELN hemizygosity revealed a 2. 5-fold increase in elastic lamellae and smooth muscle. Thus, ELN hemizygosity in mice and humans induces a compensatory increase in the number of rings of elastic lamellae and smooth muscle during arterial development. Humans are exquisitely sensitive to reduced ELN expression, developing profound arterial thickening and markedly increased risk of obstructive vascular disease.

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  • Version 1 (November 15, 1998): No description
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