TY - JOUR
T1 - Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems
AU - Weinbaum, Justin S.
AU - Broekelmann, Thomas J.
AU - Pierce, Richard A.
AU - Werneck, Claudio C.
AU - Segade, Fernando
AU - Craft, Clarissa S.
AU - Knutsen, Russell H.
AU - Mecham, Robert P.
PY - 2008/9/12
Y1 - 2008/9/12
N2 - Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1 reveals a complex phenotype that includes increased body weight and size due to excess body fat, an altered wound healing response in bone and skin, and a bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils develop normally and show normal function. The penetrance of MAGP-1-null phenotypes is highly variable and mouse strain-dependent, suggesting the influence of modifier genes. MAGP-1 was found to bind active transforming growth factor-β (TGF-β) and BMP-7 with high affinity, suggesting that it may be an important modulator of microfibril-mediated growth factor signaling. Many of the phenotypic traits observed in MAGP-1-deficient mice are consistent with loss of TGF-β function and are generally opposite those associated with mutations in fibrillin-1 that result in enhanced TGF-β signaling. Increased body size and fat deposition in MAGP-1-mutant animals are particularly intriguing given the localization of obesity traits in humans to the region on chromosome 1 containing the MAGP-1 gene.
AB - Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1 reveals a complex phenotype that includes increased body weight and size due to excess body fat, an altered wound healing response in bone and skin, and a bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils develop normally and show normal function. The penetrance of MAGP-1-null phenotypes is highly variable and mouse strain-dependent, suggesting the influence of modifier genes. MAGP-1 was found to bind active transforming growth factor-β (TGF-β) and BMP-7 with high affinity, suggesting that it may be an important modulator of microfibril-mediated growth factor signaling. Many of the phenotypic traits observed in MAGP-1-deficient mice are consistent with loss of TGF-β function and are generally opposite those associated with mutations in fibrillin-1 that result in enhanced TGF-β signaling. Increased body size and fat deposition in MAGP-1-mutant animals are particularly intriguing given the localization of obesity traits in humans to the region on chromosome 1 containing the MAGP-1 gene.
UR - http://www.scopus.com/inward/record.url?scp=54449085747&partnerID=8YFLogxK
U2 - 10.1074/jbc.M709962200
DO - 10.1074/jbc.M709962200
M3 - Article
C2 - 18625713
AN - SCOPUS:54449085747
VL - 283
SP - 25533
EP - 25543
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 37
ER -