Deficiency in microfibril-associated glycoprotein-1 (MAGP-1) leads to complex phenotypes in multiple organ systems.
J Biol Chem. 2008 Jul 14;
Authors: Weinbaum JS, Broekelmann TJ, Pierce RA, Werneck CC, Segade F, Craft CS, Knutsen RH, Mecham RP
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 TGF-ss 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-ss function and are generally opposite those associated with mutations in fibrillin-1 that result in enhanced TGF-ss 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.
PMID: 18625713 [PubMed - as supplied by publisher]
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PubMed: BMP-7
NCBI: db=PubMed; Term=BMP-7
