Immunolocalization studies have shown that
fibrillin-1 is distributed ubiquitously in the connective tissue space from early embryonic times through old age. When mutated, the gene for
fibrillin-1 (FBN1) causes the
Marfan syndrome, a common inherited disorder of connective tissue. The multiple manifestations of the
Marfan syndrome reflect the known distribution of
fibrillin-1 in cardiovascular, musculoskeletal, ocular, and dermal tissues. In this study, a mouse model of
Marfan syndrome in which
fibrillin-1 is truncated and tagged with green fluorescence was used to estimate the relative abundance of
fibrillin-1 in developing tissues. In embryonic tissues, the aorta was the only tissue in which
fibrillin-1 green fluorescence was detectable. Other arteries gained detectable
fibrillin-1 green fluorescence just after birth.
Fibrillin-1 fluorescence was observed at later postnatal times in the lung, skin, perichondrium, tendon, and ocular tissues, while other tissues remained negative. These results indicated that tissues most affected in the
Marfan syndrome are the tissues in which
fibrillin-1 is most abundant. Focus was placed on the aorta, since
aortic disease is life threatening in the
Marfan syndrome and
fibrillin-1 green fluorescence was most abundant in this tissue.
Fibrillin-1 green fluorescence and immunostaining showed that
fibrillin-1 is within aortic medial elastic lamellae. Endothelial-specific compared to smooth muscle-specific
fibrillin-1 green fluorescence, together with light microscopic analyses of fragmentation of aortic elastic lamellae, demonstrated that smooth muscle cell mutated
fibrillin-1 contributed most to progressive aortic fragmentation. However, these studies also indicated that other cells, possibly endothelial cells, also contribute to this aortic pathology. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.