| First Author | Hale JS | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 4 | Pages | e10127 |
| PubMed ID | 20405040 | Mgi Jnum | J:160149 |
| Mgi Id | MGI:4453507 | Doi | 10.1371/journal.pone.0010127 |
| Citation | Hale JS, et al. (2010) Cell-extrinsic defective lymphocyte development in Lmna(-/-) mice. PLoS One 5(4):e10127 |
| abstractText | BACKGROUND: Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/-) mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/-) mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. PRINCIPAL FINDINGS: Lmna(-/-) mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/-) bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+) and CD8(+) T cells. Transplantation of Lmna(-/-) neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development. CONCLUSIONS: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/-) mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/-) mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice. |
