Fus^tm2.1Emcf

The mouse gene sequence was modified to reproduce an amyotrophic lateral sclerosis- (ALS-) associated human mutation (p.G466VfsX14) in which an A-to-G substitution occurred in the exon 14 splice acceptor sequence. This causes exon 14 to be skipped, leading to a reading frameshift and incorporation of 14 miscoded amino acids from exon 15 (the final exon) before an early termination codon is encountered. The same splice-acceptor substitution was introduced into the mouse gene, and the coding sequence of mouse exon 15 was humanized by four nucleotide substitutions and an ATTA insertion so that the resulting protein would contain the same incorrect C-terminal 14 amino acids. This was accomplished using the same targeting construct as for Fustm1.1Emcf. A single FRT site marks the position where a neomycin selection cassette was deleted by Flp recombinase. (J:249965)