The 10-nm microfibrils are extracellular matrix aggregates of both elastic and nonelastic tissues. Very little is known about the composition and assembly of microfibrils, chiefly because of their highly insoluble nature. Among of the best characterized microfibrillar components is a 350-kDa glycoprotein, fibrillin. We and others recently cloned part of the fibrillin cDNA, mapped the gene to chromosome 15 (Fib 15), and established casual relationship between Fib 15 mutations and pleiotropic manifestations of Marfan syndrome. As a result of our cloning experiments, we also identified a fibrillin-like transcript whose gene resides on chromosome 5 (Fib 5). The second fibrillin locus was linked to congenital constractural arachnodactyly. This connective tissue disorder shares some of the skeletal manifestations of Marfan syndrome, in addition to displaying distinctive abnormalities of the joint and the external ear. We interpreted such a dual association between phenotypically related disorders and structurally related proteins as suggesting that the fibrillins may have distinct functions in different tissues, albeit both part of morphologically similar or identical aggregates. It is our long-term goal to test this hypothesis and, accordingly, in this application we describe experiments aimed at characterizing the structure, localization and pattern of expression of the Fib 5 gene product. Aside from elucidating new aspects of connective tissue pathophysiology, this descriptive work provides the basis of future investigations on the function and regulation of this newly discovered gene.
Showing the most recent 10 out of 33 publications
