The transactivating response region DNA binding protein 43 (TDP-43) p.Q331K mutation (TDP-43 Q331K) has previously been identified in ALS as a disease-causing mutation with neurotoxicity.
The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43.
Ectopic expression of ALS-associated mutant human TDP-43 (hTDP-43(M337V) and hTDP-43(Q331K)) produces a less severe SOP phenotype than hTDP-43(WT), indicating a partial loss of function of mutant hTDP-43.