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Objective To explore the biological functions of retinoic acid-inducible gene-I(RIG-I) in vivo through phenotype analysis of RIG-I knockout mice. Methods The gene expression of RIG-Ⅰ in various tissues of mice was examined with Northern blotting and semi-quantitative RT-PCR.The phenotypes observed included body weight measurement,differential count of peripheral blood cells,metabolic parameters measurement and histopathologic examination. ResultsRIG-Ⅰ expressed in various tissues of mice with different levels.No gross developmental abnormalities and expected maturation arrest in granulocytic differentiation were observed in RIG-Ⅰ knockout mice.However,RIG-Ⅰ knockout mice exhibited an unexpected increase in the ratios of neutrophiles to lymphocytes in peripheral blood and increased susceptibility to bacteria infection. Conclusion RIG-Ⅰ may play an important role in immune regulation in mice.
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<p><b>OBJECTIVE</b>In order to investigate the leukemogenic potential of NUP98-HOXA9 fusion gene in vivo.</p><p><b>METHODS</b>Molecular cloning technology was used to construct NUP98-HOXA9 transgenic plasmid and NUP98-HOXA9 transgenic mice were generated. The genotype and phenotype of the NUP98-HOXA9 transgenic mice were analyzed by PCR, RT-PCR and colony-forming assay. The effect of N-ethyl-N-nitrosourea (ENU) stimulation on the transgenic mice was analyzed by peripheral blood count, bone marrow (BM) cells morphology pathological examination.</p><p><b>RESULTS</b>The transgenic expression was detected in 5 independent lines of NUP98-HOXA9 transgenic mice, but no expected phenotypes was found in 2 year follow-up. Upon ENU stimulation, 2 of 10 transgenic mice developed myeloid leukemia, suggesting that NUP98-HOXA9 transgenic mice have increased susceptibility to ENU mutagenesis in leukemogenesis.</p><p><b>CONCLUSION</b>The fusion gene expressed in BM cells of NUP98-HOXA9 transgenic mice. It seems that the expression of the fusion gene is insufficient to trigger leukemogenesis. However, the increased susceptibility to ENU mutagenesis suggests that NUP98-HOXA9 fusion gene might play a potential role in leukemogenesis.</p>
Asunto(s)
Animales , Femenino , Humanos , Masculino , Ratones , Células de la Médula Ósea , Metabolismo , Patología , Modelos Animales de Enfermedad , Etilnitrosourea , Regulación Leucémica de la Expresión Génica , Genotipo , Proteínas de Homeodominio , Genética , Leucemia Mieloide , Sangre , Genética , Ratones Transgénicos , Proteínas de Complejo Poro Nuclear , Genética , Proteínas de Fusión Oncogénica , Genética , Fenotipo , Plásmidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TransfecciónRESUMEN
<p><b>OBJECTIVE</b>In order to investigate the leukemogenic potential of NUP98-PMX1 fusion gene in vivo.</p><p><b>METHODS</b>NUP98-PMX1 transgenic mice were generated, in which the fusion gene was driven by hCG promoter and expressed in myeloid cells at early stage of differentiation. Molecular cloning technology was used to construct NUP98-PMX1 transgenic plasmid. The genotype and phenotype of the NUP98-PMX1 transgenic mice were analyzed by PCR, RT-PCR, peripheral blood count (PBC), bone marrow (BM) cells morphology and pathological examination.</p><p><b>RESULTS</b>NIH3T3 cells transfected with NUP98-PMX1 fusion gene grew faster, formed colonies in soft agar, and developed tumors in 10 inoculated nude mice. Among 8 disordered NUP98-PMX1 transgenic mice, 4 developed myeloid leukemia-like phenotype, including 3 resembling human chronic myeloid leukemia.</p><p><b>CONCLUSION</b>NUP98-PMX1 has oncogenic activity and plays a crucial role in leukemogenesis.</p>