| First Author | Bérubé NG | Year | 2005 |
| Journal | J Clin Invest | Volume | 115 |
| Issue | 2 | Pages | 258-67 |
| PubMed ID | 15668733 | Mgi Jnum | J:95953 |
| Mgi Id | MGI:3528132 | Doi | 10.1172/JCI22329 |
| Citation | Berube NG, et al. (2005) The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. J Clin Invest 115(2):258-67 |
| abstractText | Mutations in genes encoding chromatin-remodeling proteins, such as the ATRX gene, underlie a number of genetic disorders including several X-linked mental retardation syndromes; however, the role of these proteins in normal CNS development is unknown. Here, we used a conditional gene-targeting approach to inactivate Atrx, specifically in the forebrain of mice. Loss of ATRX protein caused widespread hypocellularity in the neocortex and hippocampus and a pronounced reduction in forebrain size. Neuronal 'birthdating' confirmed that fewer neurons reached the superficial cortical layers, despite normal progenitor cell proliferation. The loss of cortical mass resulted from a 12-fold increase in neuronal apoptosis during early stages of corticogenesis in the mutant animals. Moreover, cortical progenitors isolated from Atrx-null mice undergo enhanced apoptosis upon differentiation. Taken together, our results indicate that ATRX is a critical mediator of cell survival during early neuronal differentiation. Thus, increased neuronal loss may contribute to the severe mental retardation observed in human patients. |
