TY - JOUR
T1 - Characterization of mutated protein encoded by partially duplicated fibrillin-1 gene in tight skin (TSK) mice
AU - Saito, Shinichiro
AU - Nishimura, Hiroyuki
AU - Brumeanu, Teodor D.
AU - Casares, Sofia
AU - Stan, Alexandru C.
AU - Honjo, Tasuku
AU - Bona, Constantin A.
N1 - Funding Information:
This work was supported by a grant from the National Institute of Health (AI 24671) to CAB and DFG grant Sta 429/2-1 to ACS.
PY - 1999/2
Y1 - 1999/2
N2 - Fibrillin-1 (Fbn-1) is a ubiquitous protein present in the extracellular matrix of various organs and it is a major component of microfibrils embedded in the core of elastic fibers. In humans, mutations or deletions of the Fbn- 1 gene are associated with several genetic disease. In addition, several microsatellite alleles near Fbn-1 gene were found associated with diffuse scleroderma. In TSK/+mice, which develop a scleroderma-like syndrome, the Fbn-1 gene exhibits an inframe duplication of exons 17-40. In this study, we report that the synthesis and secretion of wild-type Fbn-1 in TSK/+ is higher than that of the mutated Fbn-1 protein excluding the possibility that TSK genetic defect is due to a loss of the wild-type allele. We also demonstrate for the first time that TGF-β, which plays a crucial role in skin fibrosis, binds to both wild-type Fbn-1 and mutated Fbn-1. The amount of bound TGF-β was higher in mutated than wild-type Fbn-1 and appears related to the number of TGF-β binding motifs.
AB - Fibrillin-1 (Fbn-1) is a ubiquitous protein present in the extracellular matrix of various organs and it is a major component of microfibrils embedded in the core of elastic fibers. In humans, mutations or deletions of the Fbn- 1 gene are associated with several genetic disease. In addition, several microsatellite alleles near Fbn-1 gene were found associated with diffuse scleroderma. In TSK/+mice, which develop a scleroderma-like syndrome, the Fbn-1 gene exhibits an inframe duplication of exons 17-40. In this study, we report that the synthesis and secretion of wild-type Fbn-1 in TSK/+ is higher than that of the mutated Fbn-1 protein excluding the possibility that TSK genetic defect is due to a loss of the wild-type allele. We also demonstrate for the first time that TGF-β, which plays a crucial role in skin fibrosis, binds to both wild-type Fbn-1 and mutated Fbn-1. The amount of bound TGF-β was higher in mutated than wild-type Fbn-1 and appears related to the number of TGF-β binding motifs.
UR - http://www.scopus.com/inward/record.url?scp=0033009739&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(99)00035-8
DO - 10.1016/S0161-5890(99)00035-8
M3 - Article
C2 - 10403482
AN - SCOPUS:0033009739
SN - 0161-5890
VL - 36
SP - 169
EP - 176
JO - Molecular Immunology
JF - Molecular Immunology
IS - 3
ER -