The gain of splicing function has been recently demonstrated in knock-in mice carrying TDP-43 missense mutation: TDP-43 autoregulation is perturbed, leading to altered splicing of Mapt in TDP-43 Q331K knock-in mice [52]; TDP-43 M323K knock-in mice induce a novel gain of splicing activity leading to skipping of certain constitutive exons, albeit this mutation is not an ALS-linked mutation [82]; mRNAs splicing of Kcinp2, Sort1, and Sema3f is deregulated in the spinal cords of TDP-43 M337V knock-in mice [51]. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.