title: Androgenetic haploid embryonic stem cells produce live transgenic mice.
abstract: Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish and mice raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Shuai
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wan
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Dong
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Lisi
authors.initials: L
authors.lastname: Sang
authors.forename: Chunjing
authors.initials: C
authors.lastname: Feng
authors.forename: Guan-Zheng
authors.initials: GZ
authors.lastname: Luo
authors.forename: Tianda
authors.initials: T
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Libin
authors.initials: L
authors.lastname: Wang
authors.forename: Qin-Yuan
authors.initials: QY
authors.lastname: Zheng
authors.forename: Chao
authors.initials: C
authors.lastname: Sheng
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Wu
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology; D002460:Cell Line; D002467:Cell Nucleus; D002678:Chimera / Q000196:embryology / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic; D005260:Female; D006238:Haploidy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology / Q000235:genetics / Q000254:growth & development*; D023421:Models, Animal; D008957:Models, Genetic; D009865:Oocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000378:metabolism / Q000637:transplantation
chemical_list: D000728:Androgens; D015415:Biomarkers