Mutation of the gene encoding fibrillin-2 results in syndactyly in mice

摘要: Fibrillins are large, cysteine-rich glycoproteins that form microfibrils and play a central role in elastic fibrillogenesis. Fibrillin-1 fibrillin-2, encoded by FBN1 on chromosome 15q21.1 FBN2 5q23-q31, highly similar proteins. The finding of mutations the autosomal dominant microfibrillopathies Marfan syndrome (MFS) congenital contractural arachnodactyly (CCA), respectively, has highlighted their essential development homeostasis fibres. MFS is characterized cardiovascular, skeletal ocular abnormalities, CCA long, thin, flexed digits, crumpled ears mild joint contractures. Although arise throughout FBN1, those clustering within exons 24-32 associated with most severe MFS, so-called neonatal MFS. All described occur "neonatal region" FBN2. Both thought to via negative mechanism. analysis mouse demonstrated fibrillin-1 mainly engaged tissue rather than matrix assembly. In current investigation, we have analysed classical mutant shaker-with-syndactylism using positional candidate approach loss-of-function outside Fbn2 cause syndactyly mice. These results suggest phenotypes distinct from may result man as consequence