Mouse model - Ehler-Danlos syndrome (EDS IV)

Col3a1∆: a novel mouse mutation providing a model for the vascular type of Ehler-Danlos syndrome (EDS IV)

EDS IV is an autosomal dominant disorder that reduces life expectancy due to spontaneous rupture of arteries or the bowel. It is caused by mutation of the COL3A1 gene that encodes pro-alpha1 chains of type III collagen that is secreted into the extra cellular matrix.

A targeted knock out of Col3a1 has been of limited use: most homozygotes die shortly after birth, whereas heterozygotes don’t die from arterial rupture. By contrast, Col3a1∆/+ mice have a predisposition to sudden unexpected death from dissection of the thoracic aorta with a median life expectancy of 6 weeks.  The aorta dissection is not associated with elevated blood pressure, aneurysm formation or infection. Affected mice show disrupted architecture and tearing of the smooth muscle layer associated with structural abnormalities in collagen fibres. Not all Col3a1∆/+ mice succumb to arterial rupture, with males twice as likely to be affected than females. As such, this may provide an opportunity to identify genetic modifiers of the aorta dissection phenotype.

Col3a1∆ has been identified as a 185 Kb deletion which includes the promoter region and exons 1 to 39 of Col3a1 and is therefore assumed to be a null mutation.

In summary, this mutant provides an exploitable model for the vascular dissection phenotype seen in EDS IV that should help to elucidate the causes of, and possible treatments for, this disorder.

See: Smith, L.B. et al Cardiovasc Res 2011, 90 (1):182-190.

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N.B. official allele symbol for this mutation is now Col3a1m1Lsmi