Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems

Justin S. Weinbaum, Thomas J. Broekelmann, Richard A. Pierce, Claudio C. Werneck, Fernando Segade, Clarissa S. Craft, Russell H. Knutsen, Robert P. Mecham

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)25533-25543
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number37
DOIs
StatePublished - Sep 12 2008

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