marfan syndrome (MFS) is a systemic, autosomal dominant disease of connective tissue cause by mutations in the gene encoding fibrillin-1, a major component of the microfibril network of the ECM (13 , 15.
Tsk-1 mice develop tightening of the skin to the underlying tissues, due to a mutation in the gene encoding fibrillin 1. Fibrillin is a large ECM structural protein and the major component of microfibrils, found with or without associated elastin [ 17].
MFS has been associated with mutations of the gene encoding fibrillin-1 (FBN1), a major constituent of the elastic fibers.
In 1991, FBN1 (encoding fibrillin-1, a structural component of the microfibrils) was identified as the gene responsible for MFS [ 11].
Transcripts encoding fibrillins in P. tricornutum (Phatrdraft_48066 and Phatrdraft_55153, encoding PAP-fibrillin-1 and PAP-fibrillin-2) decreased 4- and 5-fold, respectively.
In 1991, mutations in the FBN1 gene (OMIM 134797), which encodes the fibrillin-1 protein, were genetically linked to the MFS phenotype [5], [6], [7].
Two such connective tissue disorders are Marfan's syndrome and Congenital Contractural Arachnodactyly (CCA), which are caused by dominant mutations in the fibrillin-1 (FBN1) and fibrillin-2 (FBN2) genes respectively [1], [2].
Hence, fibrillin-1, but not fibrillin-2, restricts TGF-β activity in the medial layer of the postnatal aorta by interacting with LTBP components of the LLC.
Fibrillin-2 is the key component of human elastic fiber in extracellular matrix.
Increased TGF-β signaling, however, upregulates Rankl production by osteoblasts, with consequent stimulation of bone resorption by osteoclasts in mice deficient in either fibrillin-1 or fibrillin-2 deficient mice [ 49, 50].
