title: Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells.
abstract: Haploid cells are amenable for genetic analysis. Recent success in the derivation of mouse haploid embryonic stem cells (haESCs) via parthenogenesis has enabled genetic screening in mammalian cells. However, successful generation of live animals from these haESCs, which is needed to extend the genetic analysis to the organism level, has not been achieved. Here, we report the derivation of haESCs from androgenetic blastocysts. These cells, designated as AG-haESCs, partially maintain paternal imprints, express classical ESC pluripotency markers, and contribute to various tissues, including the germline, upon injection into diploid blastocysts. Strikingly, live mice can be obtained upon injection of AG-haESCs into MII oocytes, and these mice bear haESC-carried genetic traits and develop into fertile adults. Furthermore, gene targeting via homologous recombination is feasible in the AG-haESCs. Our results demonstrate that AG-haESCs can be used as a genetically tractable fertilization agent for the production of live animals via injection into oocytes.
authors.affiliation: Group of Epigenetic Reprogramming, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Linyu
authors.initials: L
authors.lastname: Shi
authors.forename: Bang-An
authors.initials: BA
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Zhong
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D018390:Gene Targeting; D005821:Genetic Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009865:Oocytes / Q000166:cytology / Q000378:metabolism