Abstract
The utility of transgenes for both basic and applied studies has been augmented by the recent advent of versions that can be regulated by the addition of suitable activators. However, still more convenient would be transgenes whose expression responded appropriately to endogenous signals. The promoter of the glial fibrillary acidic protein (GFAP) gene is a candidate for this role in the central nervous system (CNS) since the GFAP gene is specifically expressed in astrocytes in the CNS and its activity is upregulated in response to almost any CNS injury. As a feasibility study, we isolated a C6 rat glioma cell line stably transfected with a lacZ reporter gene driven by the gfa2 human GFAP promoter fragment. We find that the activity of the transgene indeed responds to an environmental signal, forskolin, that induces astrocyte-like differentiation of C6 cells. We also isolated a C6 line carrying a transgene in which the gfa2 promoter directs expression of a cDNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine synthesis. This transgene should be of considerable interest for gene therapy for Parkinson's disease. We show that in this cell line both TH mRNA and protein are upregulated by forskolin. Finally, ...Continue Reading
References
Jun 25, 1990·Nucleic Acids Research·J P Morgenstern, H Land
Sep 1, 1989·Journal of Neurochemistry·K UchidaS Kohsaka
Jul 26, 1968·Science·P BendaW Sweet
Jun 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·A LamourouxJ Mallet
Jun 1, 1994·Experimental Neurology·R AntonR H Edwards
Jan 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H N LodeJ Beck
May 19, 1995·Neuroscience Letters·E Salero-CocaJ Segovia
Apr 13, 1995·Nature·S A ThomasR D Palmiter
Oct 1, 1994·Journal of Neurochemistry·J SegoviaA J Tobin
Jul 1, 1994·Brain Pathology·L F Eng, R S Ghirnikar
May 1, 1996·Experimental Neurology·C LundbergA Björklund
Mar 1, 1996·Cell Transplantation·C TornatoreE Major
Dec 1, 1996·Methods : a Companion to Methods in Enzymology·M Brenner, A Messing
Citations
Jun 18, 2011·Cellular and Molecular Neurobiology·Leticia ArreguiJose Segovia
Apr 2, 2004·Neurobiology of Disease·Absalom ZamoranoJosé Segovia
Aug 26, 1999·Life Sciences·F TrejoJ Segovia
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·N ShiW M Pardridge
Apr 20, 2006·Journal of Neurosurgery·Winan J Van HoudtZeng B Zhu
Sep 6, 2008·Neuroscience·J A BenítezJ Segovia
Dec 7, 2007·The American Journal of Pathology·Wei ZouJohnny J He
Aug 9, 2007·Brain Research Bulletin·Hugo Guerrero-CázaresSergio H Duenas-Jimenez
Mar 2, 2016·Nutritional Neuroscience·Adriana Morales-MartínezFrancisca Pérez-Severiano
Mar 31, 2000·Experimental Neurology·K A BakerI Mendez
Dec 18, 2013·Cancer Letters·Vishal Premdev SharmaMichael Eric Geusz
Jun 28, 2008·Pharmacology, Biochemistry, and Behavior·Francisca Pérez-SeverianoVinicio Granados-Soto
Oct 4, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Juan A Gonzalez-BarriosDaniel Martinez-Fong
Jul 3, 2013·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Natanael ZarcoJosé Segovia
Dec 24, 2010·Cell Transplantation·Jana Mejía-ToiberMagda Giordano
Dec 28, 2002·Journal of Neuroscience Research·Absalom ZamoranoJosé Segovia
Dec 5, 2008·Gene Therapy·I RothenaignerR Brack-Werner
Aug 2, 2013·European Journal of Gastroenterology & Hepatology·Jonathan ArauzPablo Muriel
Feb 5, 2000·Journal of Neuroscience Research·N CortezJ Segovia
Aug 7, 2008·Metabolic Brain Disease·Edgar Cano-EuropaJorge Pacheco-Rosado
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·José Segovia
Mar 8, 2006·World Journal of Gastroenterology : WJG·Gunter MaubachLang Zhuo
Apr 9, 2015·Human & Experimental Toxicology·J E Pérez-VargasP Muriel
Sep 17, 2002·Brain Research·Francisca Pérez-SeverianoJosé Segovia