Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel model of the vascular type of Ehlers–Danlos syndrome

摘要

AimsThe vascular type of Ehlers–Danlos syndrome (EDS IV) is an autosomal-dominant disorder characterized by thin translucent skin and extensive bruising. Patients with EDS IV have reduced life expectancy (median 45–50 years) due to spontaneous rupture of arteries (particularly large arteries) or bowel. EDS IV results from mutation of the COL3A1 gene, which encodes the pro-α1 chains of type III collagen that is secreted into the extracellular matrix, e.g. by smooth muscle cells. A mouse model of EDS IV produced by targeted ablation of Col3a1 has been of limited use as only 10% of homozygous animals survive to adulthood, whereas heterozygous animals do not die from arterial rupture. We report a novel, exploitable model of EDS IV in a spontaneously generated mouse line.