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Int J Med Sci ; 17(6): 815-823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218703


Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in Ipo11 gene utilized by gene trapping. The Ipo11-/- embryos showed an embryonic lethal phenotype. The Ipo11-/- embryos showed a reduced size at embryonic day 10.5 (E10.5) when compared with Ipo11+/+ or Ipo11+/- embryos and died by E11.5. Whereas Ipo11+/- mice were healthy and fertile, and there was no detectable changes in embryonic lethality and phenotype when reviewed. In the X-gal staining with the Ipo11-/- or Ipo11+/- embryos, strong X-gal staining positivity was detected systematically in the whole mount embryos at E10.5, although almost no X-gal positivity was detected at E9.5, indicating that the embryos die soon after the process of Ipo11 expression started. These results indicate that Ipo11 is essential for the normal embryonic development in mice.

Int J Med Sci ; 16(12): 1557-1563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839743


E2F3, a member of the E2F family, plays a critical role in cell cycle and proliferation by targeting downstream, retinoblastoma (RB) a tumor suppressor family protein. The purpose of this study, was to investigate the role and function of E2F3 in vivo. We examined phenotypic abnormalities, by deletion of the E2f3 gene in mice. Complete ablation of the E2F3 was fully penetrant, in the pure C57BL/6N background. The E2f3+/ - mouse embryo developed normally without fatal disorder. However, they exhibited reduced body weight, growth retardation, skeletal imperfection, and poor grip strength ability. Findings suggest that E2F3 has a pivotal role in muscle and bone development, and affect normal mouse growth.

Desenvolvimento Ósseo/genética , Fator de Transcrição E2F3/genética , Desenvolvimento Embrionário/genética , Músculo Esquelético/crescimento & desenvolvimento , Animais , Apoptose/genética , Peso Corporal/genética , Ciclo Celular/genética , Proliferação de Células/genética , Embrião de Mamíferos , Humanos , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Fenótipo
Biotechniques ; 59(1): 34-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26156782


The use of secondary or reprogrammable cells in the production of induced pluripotent stem cells (iPSCs) circumvents random infection by various viral particles and random, uncontrollable integrations of the viral genomes into different genomic loci. We have developed a convenient method for repeatedly producing genetically identical secondary fibroblasts via teratoma formation using pre-existing iPSCs. The iPSCs used in this study carried doxycycline (Dox)-inducible transgenes for four transcription factors in their genome. Teratoma-derived primary cells (TOFs) were obtained in a huge amount during the culture of teratomas and showed good ability to form iPSCs similar to that of regular secondary fibroblasts. Immunohistochemistry analysis demonstrated the potential of TOF-derived iPSCs to differentiate into all three germ layers. The gene expression profiles of these TOFs and their iPSCs closely mimicked those of regular embryonic fibroblasts and embryonic stem cells/iPSCs, respectively. The possibility that the iPSCs were derived from a small part of pluripotent cells lurking in the TOF population was precluded by the observation of doxycycline-dependent and PluriSin (a compound selectively eliminating pluripotent cells)- independent formations of iPSCs. Our results showed that the TOFs retained the capability to mediate cellular reprogramming, similar to that of regular secondary fibroblasts.

Técnicas de Cultura de Células , Técnicas de Reprogramação Celular , Fibroblastos/citologia , Teratoma/patologia , Animais , Imuno-Histoquímica , Células-Tronco Pluripotentes Induzidas , Camundongos SCID , Transgenes
J Korean Med Sci ; 21(5): 891-6, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17043425


Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.

Estrogênios/farmacologia , Regulação Neoplásica da Expressão Gênica , Genes ras , Inibidores do Crescimento/genética , Histona Desacetilases/fisiologia , Neoplasias Hepáticas/genética , Animais , Proliferação de Células , Receptor alfa de Estrogênio/análise , Feminino , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fatores Sexuais , Transdução de Sinais