title: Rapidly generating knockout mice from H19-Igf2 engineered androgenetic haploid embryonic stem cells.
abstract: Haploid mammalian embryonic stem cells (ESCs) hold great promise for functional genetic studies and assisted reproduction. Recently, rodent androgenetic haploid ESCs (AG-haESCs) were generated from androgenetic blastocysts and functioned like sperm to produce viable offspring via the intracytoplasmic AG-haESCs injection into oocytes. However, the efficiency of this reproduction was very low. Most pups were growth-retarded and died shortly after birth, which is not practical for producing knockout animals. Further investigation suggested a possible link between the low birthrate and aberrant expression of imprinted genes. Here, we report the high-frequency generation of healthy, fertile mice from H19-Igf2 imprinting-locus modified AG-haESCs, which maintained normal paternal imprinting and pluripotency. Moreover, it is feasible to perform further genetic manipulations in these AG-haESCs. Our study provides a reliable and efficient tool to rapidly produce gene-modified mouse models and will benefit reproductive medicine in the future.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Center for Experimental Animal Research, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100005, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
keywords: AG-haESCs; Haploid ES cells; ICAHCI; gene-modified mice; imprinted gene