Fertile androgenetic mice generated by targeted epigenetic editing of imprinting control regions

• 成果类型: Article
• 署名作者: Wei, Yanchang; Yue, Tao; Wang, Yuanyuan; Yang, Yan
• 署名单位: Shanghai Jiao Tong University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14043
• DOI: 10.1073/pnas.2425307122
• 发表日期: 2025-07-08
• 关键词: dna methylation; x-chromosome; grb10 genes; snrpn gene; cpg island; mouse; expression; deletion; GROWTH; rna

摘要

Each new mammalian life begins with the fusion of an oocyte and a sperm to produce a fertilized egg containing two sets of genomes, one from the mother and one from the father. Androgenesis, a way for producing offspring solely from male genetic material, is limited in mammals, presumably due to barriers arising from genomic imprinting, an epigenetic mechanism leading to monoallelic gene expression. Here, we report adult mammalian offspring derived from the genetic material of two sperm cells. These mice, which we refer to as androgenetic mice, were produced via targeted DNA methylation editing of seven sperm cells were injected into an enucleated oocyte to form putatively diploid embryos. Allele- specific epigenetic editing was achieved by injecting guide RNAs with protospacer adjacent motif (PAM) sequences designed to match one allele but not the other. The birth of androgenetic mice that were able to develop to adulthood demonstrates that mammalian androgenesis is achievable by targeted epigenetic remodeling of a few defined ICRs.