Production of a heterozygous exon skipping model of common marmosets using gene-editing technology

Lab Anim (NY). 2024 Sep;53(9):244-251. doi: 10.1038/s41684-024-01424-0. Epub 2024 Aug 30.

Abstract

Nonhuman primates (NHPs), which are closely related to humans, are useful in biomedical research, and an increasing number of NHP disease models have been reported using gene editing. However, many disease-related genes cause perinatal death when manipulated homozygously by gene editing. In addition, NHP resources, which are limited, should be efficiently used. Here, to address these issues, we developed a method of introducing heterozygous genetic modifications into common marmosets by combining Platinum transcription activator-like effector nuclease (TALEN) and a gene-editing strategy in oocytes. We succeeded in introducing the heterozygous exon 9 deletion mutation in the presenilin 1 gene, which causes familial Alzheimer's disease in humans, using this technology. As a result, we obtained animals with the expected genotypes and confirmed several Alzheimer's disease-related biochemical changes. This study suggests that highly efficient heterozygosity-oriented gene editing is possible using TALEN and oocytes and is an effective method for producing genetically modified animals.

MeSH terms

  • Alzheimer Disease / genetics
  • Animals
  • Animals, Genetically Modified / genetics
  • Callithrix* / genetics
  • Disease Models, Animal
  • Exons*
  • Female
  • Gene Editing* / methods
  • Heterozygote*
  • Oocytes / metabolism
  • Presenilin-1* / genetics
  • Transcription Activator-Like Effector Nucleases* / genetics

Substances

  • Transcription Activator-Like Effector Nucleases
  • Presenilin-1