{"title":"利用基因编辑技术制作普通狨猴杂合外显子缺失模型","authors":"Kenya Sato, Hiroki Sasaguri, Wakako Kumita, Tetsushi Sakuma, Tomoe Morioka, Kenichi Nagata, Takashi Inoue, Yoko Kurotaki, Naomi Mihira, Michihira Tagami, Ri-ichiroh Manabe, Kokoro Ozaki, Yasushi Okazaki, Takashi Yamamoto, Makoto Suematsu, Takaomi C. Saido, Erika Sasaki","doi":"10.1038/s41684-024-01424-0","DOIUrl":null,"url":null,"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. This study shows that using gene-editing technology in oocytes using Platinum TALEN is an effective method for producing genetically modified marmosets by exon skipping.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01424-0.pdf","citationCount":"0","resultStr":"{\"title\":\"Production of a heterozygous exon skipping model of common marmosets using gene-editing technology\",\"authors\":\"Kenya Sato, Hiroki Sasaguri, Wakako Kumita, Tetsushi Sakuma, Tomoe Morioka, Kenichi Nagata, Takashi Inoue, Yoko Kurotaki, Naomi Mihira, Michihira Tagami, Ri-ichiroh Manabe, Kokoro Ozaki, Yasushi Okazaki, Takashi Yamamoto, Makoto Suematsu, Takaomi C. Saido, Erika Sasaki\",\"doi\":\"10.1038/s41684-024-01424-0\",\"DOIUrl\":null,\"url\":null,\"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. This study shows that using gene-editing technology in oocytes using Platinum TALEN is an effective method for producing genetically modified marmosets by exon skipping.\",\"PeriodicalId\":17936,\"journal\":{\"name\":\"Lab Animal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41684-024-01424-0.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lab Animal\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.nature.com/articles/s41684-024-01424-0\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lab Animal","FirstCategoryId":"97","ListUrlMain":"https://www.nature.com/articles/s41684-024-01424-0","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
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. This study shows that using gene-editing technology in oocytes using Platinum TALEN is an effective method for producing genetically modified marmosets by exon skipping.
期刊介绍:
LabAnimal is a Nature Research journal dedicated to in vivo science and technology that improves our basic understanding and use of model organisms of human health and disease. In addition to basic research, methods and technologies, LabAnimal also covers important news, business and regulatory matters that impact the development and application of model organisms for preclinical research.
LabAnimal's focus is on innovative in vivo methods, research and technology covering a wide range of model organisms. Our broad scope ensures that the work we publish reaches the widest possible audience. LabAnimal provides a rigorous and fair peer review of manuscripts, high standards for copyediting and production, and efficient publication.