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Unravelling the discriminative pathomechanisms for biglycan-related aortopathy and spondylo-epi-metaphyseal dysplasia.
Progressive dilatation of the aorta leads to the development of thoracic aortic aneurysms, which are often asymptomatic but predispose to aortic dissection and rupture. The latter are associated with high mortality rates. In 2016, I identified loss-of-function (LOF) mutations in BGN, an X-linked gene, as a novel cause of a severe syndromic form of thoracic aortic aneurysms and dissections (TAAD) and is now designated as Meester-Loeys syndrome (MLS). In parallel with my observations in aneurysmal phenotypes, missense mutations in BGN were described as the cause of an X-linked spondylo-epi-metaphyseal dysplasia (X-SEMD). The general aim of this proposal is to unravel the underlying mechanisms of different BGN mutations in the development of two very distinctive phenotypes: syndromic TAAD (MLS) and X-SEMD. We aim to further unravel these pathomechanisms using detailed phenotypical characterisation and transcriptomics in BALB/cA Bgn male knock-out (LOF) and knock-in (gain-of-function?) mouse models, respectively.
Date:1 Apr 2019 → 30 Mar 2020
Keywords:KNOCK OUT MOUSE, THORACIC AORTIC ANEURYSM, BIGLYCAN, KNOCK IN MOUSE