High-level regulated expression of the human G6PD gene in transgenic mice |
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| Affiliation: | 1. Division of Trauma, Critical Care, Burns and Acute Care Surgery, Department of Surgery, School of Medicine, University of California San Diego, 92093, La Jolla, CA, USA;2. São Carlos Institute of Chemistry, University of São Paulo, São Paulo, Brazil;3. Department of Neurosciences, School of Medicine, University of California San Diego, 92093, La Jolla, CA, USA;1. Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, 35392 Giessen, Germany;2. Max Planck Institute for Medical Research, 69120 Heidelberg, Germany;1. Department of Biosciences, Università degli Studi di Milano, Milan, Italy;2. Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy;3. Laboratory of Neuroepigenetics, Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Centro di Eccellenza per le Malattie Neurodegenerative (CEND), Università degli Studi di Milano, Milan, Italy;4. Department of Evolutionary Biology, University of Siena, Siena, Italy;5. Department of Medical Biotechnology and Translational Medicine, Clinica Ortopedica e Traumatologica, Università degli Studi di Milano, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;1. Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan;2. Department of Respiratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan;3. Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kitasato University, Kanagawa, Japan;4. Department of Pathology, School of Medicine, Kitasato University, Kanagawa, Japan |
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| Abstract: | The glucose-6-phosphate dehydrogenase-encoding gene (G6PD) belongs to a group with constitutive expression in all tissues. The regulation of these housekeeping genes is poorly understood, as compared to what is known about many genes whose expression is restricted to a particular tissue or stage of development, and which are often regulated by locus control regions (LCR) able to act over wide distances. In order to identify sequences in human G6PD which are necessary for its expression, we have generated transgenic mice carrying a 20-kb G6PD construct, including only 2.5 kb of upstream and 2.0 kb of downstream flanking sequence. All mice which carried the transgene (TG) expressed it, and the levels of expression detected in a range of tissues from three independent lines of mice were comparable to that of the endogenous murine G6PD. The variation in enzyme activity from tissue to tissue was remarkably similar for both the TG and the endogenous gene, and was shown to be due in both cases to variations in the steady-state mRNA levels. |
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