tailieunhanh - Báo cáo khoa học: Targeted disruption of one of the importin a family members leads to female functional incompetence in delivery

Importinamediates the nuclear import of proteins through nuclear pore complexes in eukaryotic cells, and is common to all eukaryotes. Previous reports identified at least six importinafamily genes in mice. Although these isoforms show differential binding to various import cargoes in vitro, the in vivo physiological roles of these mammalian importina isoforms remain unknown. | IFEBS Journal Targeted disruption of one of the importin a family members leads to female functional incompetence in delivery Tetsuji Moriyama1 Masahiro Nagai2 Masahiro Oka1 2 3 Masahito Ikawa4 Masaru Okabe4 and Yoshihiro Yoneda1 2 3 1 Department of Frontier Biosciences Graduate Schoolof Frontier Biosciences Osaka University Japan 2 Department of Biochemistry Graduate Schoolof Medicine Osaka University Japan 3 JST CREST Graduate Schoolof Frontier Biosciences Osaka University Japan 4 Department of ExperimentalGenome Research Research Institute for MicrobialDiseases Osaka University Japan Keywords estrogen gene knockout importin a nuclear transport reproduction Correspondence Y. Yoneda Department of Frontier Biosciences Osaka University Graduate School of Frontier Biosciences Osaka University 1-3 Yamada-oka Suita Osaka 565-0871 Japan Fax 81 6 6879 4609 Tel 81 6 6879 4606 E-mail yyoneda@ Received 30 October 2010 revised 10 February 2011 accepted 22 February 2011 doi Importin a mediates the nuclear import of proteins through nuclear pore complexes in eukaryotic cells and is common to all eukaryotes. Previous reports identified at least six importin a family genes in mice. Although these isoforms show differential binding to various import cargoes in vitro the in vivo physiological roles of these mammalian importin a isoforms remain unknown. Here we generated and examined importin a5 knockout impa5 mice. These mice developed normally and showed no gross histological abnormalities in most major organs. However the ovary and uterus of impaĩ 7 female mice exhibited hypoplasia. Furthermore we found that impa5 female mice had a 50 decrease in serum progesterone levels and a 57 decrease in progesterone receptor mRNA levels in the ovary. Additionally impa5 uteruses that were treated with exogenous gonadotropins displayed hypertrophy similarly to progesterone receptor-deficient mice. Although these mutant female mice could