FIGURE 1.

Generation of C9orf72 hexanucleotide repeat expansion knockin rats. The DNA sequence of the C9orf72 exon1 region from human, mouse and rat were compared (A). A 1047 bp human DNA fragment containing 80 G₄C₂ repeats, exon1a and exon1b, and flanking sequences was used to replace the entire C9orf72 exon1 of the rat using CRISPR/Cas9 (B). The C9orf72 protein expression levels were detected by western blot and quantitated by densitometry using NIH Image J software (C and D, n = 3, 2 males and 1 female, ***P < .001 vs respective controls)