Fibrillin-1 in the Vasculature: In Vivo Accumulation of eGFP-Tagged Fibrillin-1 in a Knockin Mouse Model. Anat Rec (Hoboken) 2020 Jun;303(6):1590-1603
Date
06/30/2019Pubmed ID
31251835DOI
10.1002/ar.24217Scopus ID
2-s2.0-85069937293 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Charbonneau NL, Manalo EC, Tufa SF, Carlson EJ, Carlberg VM, Keene DR, Sakai LYAuthor
Valerie M. Carlberg MD Associate Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArteries
Disease Models, Animal
Endothelial Cells
Endothelium, Vascular
Fibrillin-1
Marfan Syndrome
Mice
