Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have generated transgenic mice expressing human granulocyte macrophage-colony stimulating factor (hGM-CSF) in urine. In particular, the expression plasmid DNA containing mouse uroplakin II promoter was used to direct uroepithelium-specific transcription of transgene. In this study, hGM-CSF transcript was detected only in bladder uroepithelium as determined by northern blot analysis. Furthermore, hGM-CSF protein was detected in the suprabasal layer of the uroepithelium and ureter by immunohistochemistry. The hGM-CSF was secreted into urine at high level (up to 180 ng/ml), and enhanced proliferation of hGM-CSF-dependent human acute monocyte leukemic cells, suggesting that transgenic urine-derived hGM-CSF was bioactive. This is the first case of demonstrating biological activity of a cytokine produced in the urine of a transgenic animal. Our results demonstrate that bladder can be used as a bioreactor to produce biologically important substances. In addition, it suggests a potential application of bladder expression system to livestock for high-yield production of pharmaceuticals.
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PMID:Expression of recombinant human granulocyte macrophage-colony stimulating factor (hGM-CSF) in mouse urine. 1143 76

We have generated transgenic mice that expressed human granulocyte-colony stimulating factor (hG-CSF) in their urine. In particular, the expression plasmid DNA containing mouse uroplakin II promoter was used to direct the uroepithelium-specific transcription of the transgene. In this study, the hG-CSF transcript was detected only in bladder, as was determined by RT-PCR analysis. Furthermore, hG-CSF protein was detected in the suprabasal layer of the uroepithelium and ureter, as was demonstrated by immunohistochemistry. The hG-CSF was secreted into urine at a high level (approx. 500 pg/ml), and it was able to enhance the proliferation of DMSO treated HL-60 cells, suggesting that the transgenic urine-derived hG-CSF was bioactive. However, the recombinant hG-CSF was leaked to peripheral circulation system. To examine the relationship between hG-CSF in the blood stream and the proliferation of hematopoietic cells, we tested the transgenic mouse blood with hematocrit analysis. An increase of the total number of neutrophils in the transgenic mice peripheral blood was not observed; therefore, the leakage of human G-CSF can probably be expected to do no harm to the transgenic mouse. Our results demonstrate that bladder can be safely used as a bioreactor to produce biologically important substances such as recombinant G-CSF.
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PMID:Transgene expression of biological active recombinant human granulocyte-colony stimulating factor (hG-CSF) into mouse urine. 1616 42