Fig 1. HDR knockin of point mutations in zebrafish using the CRISPR/Cas9 system with ssODN templates.

Schematic representation of zebrafish tdp-43 (A) and fus (B) and locations of point mutations encoding missense mutations generated by HDR (top). L, nuclear localization sequences; E, nuclear export sequences; RRM, RNA recognition motifs; ZnF, zinc finger motif. Exon coding sequences (middle). Comparisons of zebrafish gRNA target sites with human coding sequences (bottom). Note the high amino acid sequence homologies between human and zebrafish proteins. ALS-causing point mutations (red) encoding missense mutations TARDBP^A382T and FUS^R521H are indicated in the human sequences and analogous point mutations are noted in the zebrafish genes (tardbp^A379T and fus^R536H).