Effects of CRISPR/Cas9 dosage on TICAM1 and RBL gene mutation rate, embryonic development, hatchability and fry survival in channel catfish

Sci Rep. 2018 Nov 7;8(1):16499. doi: 10.1038/s41598-018-34738-4.

Abstract

The current study was conducted to assess the effects of microinjection of different dosages of guide RNA (gRNA)/Cas9 protein on the mutation rate, embryo survival, embryonic development, hatchability and early fry survival in channel catfish, Ictalurus punctatus. Guide RNAs targeting two of the channel catfish immune-related genes, toll/interleukin 1 receptor domain-containing adapter molecule (TICAM 1) and rhamnose binding lectin (RBL) genes, were designed and prepared. Three dosages of gRNA/Cas9 protein (low, 2.5 ng gRNA/7.5 ng Cas9, medium, 5 ng gRNA/15 ng Cas9 and high, 7.5 ng gRNA/22.5 ng Cas9) were microinjected into the yolk of one-cell embryos. Mutation rate increased with higher dosages (p < 0.05). Higher dosages increased the mutation frequency in individual embryos where biallelic mutations were detected. For both genes, microinjection procedures increased the embryo mortality (p < 0.05). Increasing the dosage of gRNA/Cas9 protein increased the embryo mortality and reduced the hatching percent (p < 0.05). Embryonic development was delayed when gRNAs targeting RBL gene were injected. Means of fry survival time were similar for different dosages (p > 0.05). The current results lay the foundations for designing gene editing experiments in channel catfish and can be used as a guide for other fish species.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / genetics*
  • Animals
  • Base Sequence
  • CRISPR-Cas Systems*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics*
  • Congenital Abnormalities / diagnosis
  • Congenital Abnormalities / genetics
  • Embryonic Development / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Ictaluridae / physiology*
  • Mortality
  • Mutation Rate*
  • Mutation*
  • Open Reading Frames
  • Phenotype
  • Reproduction / genetics

Substances

  • Adaptor Proteins, Vesicular Transport
  • Chromosomal Proteins, Non-Histone