| First Author | Kraemer BC | Year | 2010 |
| Journal | Acta Neuropathol | Volume | 119 |
| Issue | 4 | Pages | 409-19 |
| PubMed ID | 20198480 | Mgi Jnum | J:158641 |
| Mgi Id | MGI:4439260 | Doi | 10.1007/s00401-010-0659-0 |
| Citation | Kraemer BC, et al. (2010) Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol 119(4):409-19 |
| abstractText | Abnormal TDP-43 aggregation is a prominent feature in the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Mutations in TARDBP, the gene encoding TDP-43, cause some cases of ALS. The normal function of TDP-43 remains incompletely understood. To better understand TDP-43 biology, we generated mutant mice carrying a genetrap disruption of Tardbp. Mice homozygous for loss of TDP-43 are not viable. TDP-43 deficient embryos die about day 7.5 of embryonic development thereby demonstrating that TDP-43 protein is essential for normal prenatal development and survival. However, heterozygous Tardbp mutant mice exhibit signs of motor disturbance and muscle weakness. Compared with wild type control littermates, Tardbp (+/-) animals have significantly decreased forelimb grip strength and display deficits in a standard inverted grid test despite no evidence of pathologic changes in motor neurons. Thus, TDP-43 is essential for viability, and mild reduction in TDP-43 function is sufficient to cause motor deficits without degeneration of motor neurons. |
