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Impaired expression of importin/karyopherin beta1 leads to post-implantation lethality
Authors:Miura Katsutaka  Yoshinobu Kumiko  Imaizumi Takashi  Haruna Kyoko  Miyamoto Yoichi  Yoneda Yoshihiro  Nakagata Naomi  Araki Masatake  Miyakawa Taihei  Yamamura Ken-ichi  Araki Kimi
Institution:Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
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.
Keywords:Importin β1  Gene trap  Cre/lox site-specific recombination  Embryonic lethal
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