Visible traits demonstrate that crispant founder mice can be used for phenotypic assessment

Genetic mosaicism was common, but did not confound an animal’s phenotype when comprised of mutations that all disrupt the targeted gene. Mosaicism included short in-frame mutations, but these were sufficient to disrupt function of five genes. Several founders were compound heterozygotes carrying a null and a non-null allele (short in-frame mutation or late truncation), enabling functional assessment of the non-null allele to dissect protein function.

Our results set the stage for using crispant founders for initial phenotypic assessment in genetic screening, before selecting candidates for further study. This will dramatically reduce animal numbers.