A methionine to valine substitution at amino acid 337 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 M337V mutation is one of the most common amyotrophic lateral sclerosis-associated mutations. TARDBP remains nuclear in homozygous mice. (J:283769)