A glycine to serine substitution at amino acid 298 was introduced into exon 6 along with a FRT-flanked neomycin resistance cassette via homologous recombination. Flp-mediated recombination removed the neo selection cassette. The G298S mutation is associated with shorter progression of amyotrophic lateral sclerosis. TARDBP remains nuclear in homozygous mice. (J:283769)