title: Impaired expression of importin/karyopherin beta1 leads to post-implantation lethality.
abstract: Importin beta1 (Impbeta)/karyopherin beta1 (Kpnb1) mediates the nuclear import of a large variety of substrates. This study aimed to investigate the requirement for the Kpnb1 gene in mouse development, using a gene trap line, B6-CB-Ayu8108(GtgeoIMEG) (Ayu8108(geo)), in which the trap vector was inserted into the promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene. Ayu8108(geo/geo) homozygous embryos could develop to the blastocyst stage, but died before embryonic day 5.5, and expression of the Kpnb1 gene in homozygous blastocysts was undetectable. We also replaced the betageo gene with Impbeta cDNA through Cre-mediated recombination to rescue Impbeta expression. Homozygous mice for the rescued allele Ayu8108(Impbeta/Impbeta) were born and developed normally. These results demonstrated that the cause of post-implantation lethality of Ayu8108(geo/geo) homozygous embryos was impaired expression of the Kpnb1 gene, indicating indispensable roles of Impbeta1 in early development of mice.
authors.affiliation: Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Miura
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yoshinobu
authors.forename: Takashi
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Haruna
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.forename: Taihei
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D010065:Embryo Implantation, Delayed / Q000502:physiology*; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D028961:beta Karyopherins
chemical_list: C094999:Kpnb1 protein, mouse; D009687:Nuclear Proteins; D028961:beta Karyopherins