Impaired expression of importin/karyopherin β1 leads to post-implantation lethality

Importin β1 (Impβ)/karyopherin β1 (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-Ayu8108GtgeoIMEG (Ayu8108geo), in which the trap vector was inserted into the promoter region of the Kpnb1 gene, but in reverse orientation of the Kpnb1 gene. Ayu8108geo/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 βgeo gene with Impβ cDNA through Cre-mediated recombination to rescue Impβ expression. Homozygous mice for the rescued allele Ayu8108Impβ/Impβ were born and developed normally. These results demonstrated that the cause of post-implantation lethality of Ayu8108geo/geo homozygous embryos was impaired expression of the Kpnb1 gene, indicating indispensable roles of Impβ1 in early development of mice.