| First Author | Stallings NR | Year | 2010 |
| Journal | Neurobiol Dis | Volume | 40 |
| Issue | 2 | Pages | 404-14 |
| PubMed ID | 20621187 | Mgi Jnum | J:165985 |
| Mgi Id | MGI:4839413 | Doi | 10.1016/j.nbd.2010.06.017 |
| Citation | Stallings NR, et al. (2010) Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis 40(2):404-14 |
| abstractText | Familial ALS patients with TDP-43 gene mutations and sporadic ALS patients share common TDP-43 neuronal pathology. To delineate mechanisms underlying TDP-43 proteinopathies, transgenic mice expressing A315T, M337V or wild type human TDP-43 were generated. Multiple TDP-43 founders developed a severe early motor phenotype that correlated with TDP-43 levels in spinal cord. Three A315T TDP-43 lines developed later onset paralysis with cytoplasmic ubiquitin inclusions, gliosis and TDP-43 redistribution and fragmentation. The WT TDP-43 mouse line with highest spinal cord expression levels remains asymptomatic, although these mice show spinal cord pathology. One WT TDP-43 line with high skeletal muscle levels of TDP-43 developed a severe progressive myopathy. Over-expression of TDP-43 in vivo is sufficient to produce progressive motor phenotypes by a toxic gain of function paradigm. Transgenic mouse lines expressing untagged mutant and wild type TDP-43 under the same promoter represent a powerful new model system for studying TDP-43 proteinopathies in vivo. |
