| First Author | Kojima K | Year | 2011 |
| Journal | Kidney Int | Volume | 79 |
| Issue | 3 | Pages | 311-6 |
| PubMed ID | 20944549 | Mgi Jnum | J:186889 |
| Mgi Id | MGI:5433465 | Doi | 10.1038/ki.2010.403 |
| Citation | Kojima K, et al. (2011) Defective glycosylation of alpha-dystroglycan contributes to podocyte flattening. Kidney Int 79(3):311-6 |
| abstractText | In addition to skeletal muscle and the nervous system, alpha-dystroglycan is found in the podocyte basal membrane, stabilizing these cells on the glomerular basement membrane. Fukutin, named after the gene responsible for Fukuyama-type congenital muscular dystrophy, is a putative glycosyltransferase required for the post-translational modification of alpha-dystroglycan. Chimeric mice targeted for both alleles of fukutin develop severe muscular dystrophy; however, these mice do not have proteinuria. Despite the lack of a functional renal defect, we evaluated glomerular structure and found minor abnormalities in the chimeric mice by light microscopy. Electron microscopy revealed flattening of podocyte foot processes, the number of which was significantly lower in the chimeric compared to wild-type mice. A monoclonal antibody against the laminin-binding carbohydrate residues of alpha-dystroglycan did not detect alpha-dystroglycan glycosylation in the glomeruli by immunoblotting or immunohistochemistry. In contrast, expression of the core alpha-dystroglycan protein was preserved. There was no statistical difference in dystroglycan mRNA expression or in the amount of nephrin and alpha3-integrin protein in the chimeric compared to the wild-type mice as judged by immunohistochemistry and real-time RT-PCR. Thus, our results indicate that appropriate glycosylation of alpha-dystroglycan has an important role in the maintenance of podocyte architecture. |
