Production of a heterozygous exon skipping model of common marmosets using gene-editing technology
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.
Authors
- K. Sato (ORCID: https://orcid.org/0000-0001-6952-3799)
- Takashi Yamamoto (ORCID: https://orcid.org/0000-0001-9586-6584)
- Takashi Inoue (ORCID: https://orcid.org/0000-0003-4691-7255)
- Takaomi C. Saido (ORCID: https://orcid.org/0000-0003-1970-6903)
- Tetsushi Sakuma (ORCID: https://orcid.org/0000-0003-0396-1563)
- Erika Sasaki (ORCID: https://orcid.org/0000-0002-0415-5400)
- Makoto Suematsu (ORCID: https://orcid.org/0000-0002-7165-6336)
- Naomi Mihira
- Michihira Tagami (ORCID: https://orcid.org/0000-0002-9713-3576)
- Tomoe Morioka
- Yasushi Okazaki (ORCID: https://orcid.org/0000-0003-3241-5502)
- Wakako Kumita (ORCID: https://orcid.org/0000-0003-0284-0831)
- Yoko Kurotaki (ORCID: https://orcid.org/0000-0002-0995-0542)
- Kenichi Nagata (ORCID: https://orcid.org/0000-0001-8377-7197)
- Ri‐Ichiroh Manabe (ORCID: https://orcid.org/0000-0002-4785-4228)
- Hiroki Sasaguri (ORCID: https://orcid.org/0000-0003-2550-9156)
- Kokoro Ozaki (ORCID: https://orcid.org/0000-0001-9081-8348)
Institutions
- Hiroshima University (JP)
- Keio University (JP)
- Central Institute for Experimental Animals (JP)
- RIKEN Center for Brain Science (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Nagoya University (JP)
Publication Details
- Journal
- Lab Animal
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1038/s41684-024-01424-0
- Citations
- 9
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 2.10
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science
- RIKEN