| First Author | Li Q | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 364 |
| Issue | 2 | Pages | 208-13 |
| PubMed ID | 17942075 | Mgi Jnum | J:127430 |
| Mgi Id | MGI:3763753 | Doi | 10.1016/j.bbrc.2007.09.122 |
| Citation | Li Q, et al. (2007) Pseudoxanthoma elasticum: reduced gamma-glutamyl carboxylation of matrix gla protein in a mouse model (Abcc6-/-). Biochem Biophys Res Commun 364(2):208-13 |
| abstractText | Pseudoxanthoma elasticum (PXE), a heritable multi-system disorder manifesting with ectopic mineralization of soft connective tissues, is caused by mutations in the ABCC6/MRP6 gene/protein system, but the mechanisms how the ABCC6 mutations lead to aberrant mineralization are currently unknown. In this study, we utilized a transgenic mouse model, Abcc6-/-, to examine the mineralization processes. We focused on matrix gla protein (MGP) which has been shown to be critical, when activated by gamma-carboxylation of glutamyl residues, for prevention of unwanted mineralization. The concentration of MGP in the serum of Abcc6-/- mice was significantly reduced when compared to wild-type controls (p<0.004). More importantly, MGP isolated from the liver of Abcc6-/- mice was largely under-carboxylated and therefore possesses no activity. Finally, examination of the Abcc6-/- mice revealed association of total and under-carboxylated forms of MGP with ectopic mineralization while the gamma-carboxylated form was essentially absent. These results suggest that MGP in Abcc6-/- mice is largely in inactive form and is unable to prevent the unwanted mineralization of connective tissues in PXE. |
