title: Novel importin-alpha family member Kpna7 is required for normal fertility and fecundity in the mouse.
abstract: Nuclear importing system and nuclear factors play important roles in mediating nuclear reprogramming and zygotic gene activation. However, the components and mechanisms that mediate nuclearly specific targeting of the nuclear proteins during nuclear reprogramming and zygotic gene activation remain largely unknown. Here, we identified a novel member of the importin-α family, AW146299(KPNA7), which is predominantly expressed in mouse oocytes and zygotes and localizes to the nucleus or spindle. Mutation of Kpna7 gene caused reproductivity reduction and sex imbalance by inducing preferential fetal lethality in females. Parthenogenesis analysis showed that the cell cycle of activated one-cell embryos is loss of control and ahead of schedule but finally failed to develop into blastocyst stage. Further RT-PCR and epigenetic modification analysis showed that knocking out of Kpna7 induced abnormalities of gene expression (dppa2, dppa4, and piwil2) and epigenetic modifications (down-regulation of histone H3K27me3). Biochemical analysis showed that KPNA7 interacts with KPNB1 (importin-β1). In summary, we identified a novel Kpna7 gene that is required for normal fertility and fecundity.
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hu
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Wang
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Kou
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.affiliation: From the National Institute of Biological Sciences, Beijing 102206, China. Electronic address: gaoshaorong@nibs.ac.cn.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000502:physiology*; D005313:Fetal Death / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D055785:Gene Knockdown Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015053:Zygote / Q000166:cytology / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins
chemical_list: D060565:Argonaute Proteins; C519286:Dppa2 protein, mouse; C519287:Dppa4 protein, mouse; C553637:Kpna7 protein, mouse; C094999:Kpnb1 protein, mouse; D009687:Nuclear Proteins; C448521:Piwil2 protein, mouse; D011506:Proteins; D014157:Transcription Factors; D028901:alpha Karyopherins; D028961:beta Karyopherins