| First Author | Watanabe S | Year | 2020 |
| Journal | Mol Brain | Volume | 13 |
| Issue | 1 | Pages | 8 |
| PubMed ID | 31959210 | Mgi Jnum | J:285477 |
| Mgi Id | MGI:6393052 | Doi | 10.1186/s13041-020-0550-4 |
| Citation | Watanabe S, et al. (2020) ALS-linked TDP-43(M337V) knock-in mice exhibit splicing deregulation without neurodegeneration. Mol Brain 13(1):8 |
| abstractText | Abnormal accumulation of TAR DNA-binding protein 43 (TDP-43), a DNA/RNA binding protein, is a pathological signature of amyotrophic lateral sclerosis (ALS). Missense mutations in the TARDBP gene are also found in inherited and sporadic ALS, indicating that dysfunction in TDP-43 is causative for ALS. To model TDP-43-linked ALS in rodents, we generated TDP-43 knock-in mice with inherited ALS patient-derived TDP-43(M337V) mutation. Homozygous TDP-43(M337V) mice developed normally without exhibiting detectable motor dysfunction and neurodegeneration. However, splicing of mRNAs regulated by TDP-43 was deregulated in the spinal cords of TDP-43(M337V) mice. Together with the recently reported TDP-43 knock-in mice with ALS-linked mutations, our finding indicates that ALS patient-derived mutations in the TARDBP gene at a carboxyl-terminal domain of TDP-43 may cause a gain of splicing function by TDP-43, however, were insufficient to induce robust neurodegeneration in mice. |
