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Engineering and technology
- Genetically modified animals
Osteogenesis Imperfecta (OI), also known as ‘rittle bone disease’ is a heritable connective tissue disorder, characterized by fragile bones and high susceptibility to fracture The most prevalent types of OI (>90%) are caused by genetic defects in collagen type I and show autosomal dominant inheritance, with symptoms ranging from mild to lethal Although to some extent, the position and the type of mutation are related to the severity of the disease, very little is known about how a specific collagen type I mutation leads to a particular phenotype and why there is also a marked intra-familial variability In this project we want to disclose the molecular, cellular and ultrastructural mechanisms underlying the pathogenesis in different dominant types of OI that show different phenotypic severities Eventually, identifying the pathogenic processes that determine the variability in severity in different forms of the disorder will be crucial to develop targeted treatments To achieve our goals we will use an already available set of OI zebrafish models, carrying mutations that are similar to the ones identified in human patients, also resulting in variable severities of skeletal abnormalities Numerous studies, carried out by our lab and others have highlighted the potential of using zebrafish for the analysis of bone development and disease Eventually, our innovative approach has potential to be applied to other monogenic disorders with a variable phenotype