| First Author | Kronenberg-Tenga R | Year | 2021 |
| Journal | J Cell Sci | Volume | 134 |
| Issue | 6 | PubMed ID | 33536248 |
| Mgi Jnum | J:303793 | Mgi Id | MGI:6512295 |
| Doi | 10.1242/jcs.256156 | Citation | Kronenberg-Tenga R, et al. (2021) A lamin A/C variant causing striated muscle disease provides insights into filament organization. J Cell Sci 134(6):jcs256156 |
| abstractText | The LMNA gene encodes the A-type lamins, which polymerize into approximately 3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in LMNA cause a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts from Lmna (H222P/H222P) mice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filaments in situ and using a nuclear extraction protocol. Averaging of individual segments of filaments in Lmna (H222P/H222P) mouse fibroblasts resolved two polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure. |
