Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system

Neurobiology of Disease
B P BrooksK H Fischbeck

Abstract

Spinal and bulbar muscular atrophy (SBMA) is an inherited form of lower motor neuron degeneration caused by expansion of a CAG repeat in the androgen receptor (AR) gene. To study the mechanism by which this mutation causes neuronal pathology, we stably transfected a motor neuron hybrid cell line with human AR cDNAs containing either 24 or 65 repeats (AR24 and AR65, respectively). Both forms of receptor were able to bind ligand and activate transcription of a reporter construct equally well. Likewise, the subcellular localizations of AR24 and AR65 were similar, in both the presence and the absence of ligand. AR24- and AR65-expressing clones were phenotypically indistinguishable. They survived equally well after differentiation and were equally susceptible to damage by oxidative stress. Our studies thus demonstrate that, in a neuronal system, the expanded repeat AR functions like the normal repeat AR in several important ways. Because levels of AR65 expression were consistently lower than levels of AR24 expression, we propose that the loss of function of AR seen in SBMA may be due to decreased levels of receptor expression rather than to a difference in intrinsic properties. The postulated gain of function responsible for neurona...Continue Reading

References

Sep 1, 1991·Neuroreport·E F Salazar-GruesoH Kim
Jan 1, 1995·Life Sciences·A C Bowling, M F Beal
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·K StottM Perutz
Jan 1, 1994·Annual Review of Biochemistry·M J Tsai, B W O'Malley
May 1, 1994·In Vitro Cellular & Developmental Biology. Animal·K FukuchiG M Martin
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·M F PerutzJ T Finch
Aug 1, 1993·The Biochemical Journal·G JensterA O Brinkmann
Oct 1, 1995·Trends in Neurosciences·B P Brooks, K H Fischbeck

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Citations

Nov 26, 2003·Neuropathology and Applied Neurobiology·J D WoodP J Shaw
Oct 1, 2008·Human Molecular Genetics·Srikanth RanganathanKenneth H Fischbeck
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C A RossD R Borchelt
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·K H FischbeckD E Merry
Dec 21, 2004·Journal of Neurochemistry·T U MarronA Poletti
Jan 30, 2003·RNA·Josée DostieGideon Dreyfuss
Oct 11, 2008·Biological Chemistry·Niclas W SchifferSarah A Broadley
Jan 4, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Diane E Merry
Aug 12, 2014·Nature Neuroscience·Constanza J CortesAlbert R La Spada
Jan 13, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Naemeh PourshafieCarlo Rinaldi
Nov 24, 2001·Brain Research Bulletin·D E Merry
Jun 8, 2000·Muscle & Nerve·A P Lieberman, K H Fischbeck
Jun 5, 2003·Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi·K M AuH L Li
Nov 5, 2003·Journal of Neuroscience Research·V Tarlac, E Storey
Dec 16, 2003·The Prostate·Dacheng DingEvelyn R Barrack
Mar 23, 2000·American Journal of Medical Genetics·B GottliebM Trifiro
Aug 30, 2008·Journal of Neuroscience Research·Caroline RouleauDidier Petite
Jan 1, 2014·Orphanet Journal of Rare Diseases·Ha TrangUNKNOWN European Central Hypoventilation Syndrome Consortium
May 2, 2007·Human Molecular Genetics·Isabella PalazzoloMaria Pennuto
Sep 3, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Federica PiccioniAngelo Poletti
Jan 14, 1999·Journal of Neurochemistry·L M EllerbyD E Bredesen
Aug 15, 2020·Frontiers in Aging Neuroscience·Riccardo CristofaniAngelo Poletti
Nov 29, 2015·Journal of Molecular Neuroscience : MN·Maria Pennuto, Manuela Basso
Nov 7, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Frederick J Arnold, Diane E Merry
Jun 1, 1997·Journal of Inherited Metabolic Disease·K H Fischbeck
Jul 25, 2007·The Journal of Biological Chemistry·Jessica E YoungLisa M Ellerby
Oct 22, 2002·The Journal of Biological Chemistry·Jessica L Walcott, Diane E Merry
Mar 6, 2021·Nature Communications·Brett A McCrayCharlotte J Sumner
Jun 13, 2001·Biochemical and Biophysical Research Communications·A P LiebermanK H Fischbeck
Nov 8, 2005·Brain Research·Jin-Shu YangWei-Jun Yang
Mar 7, 2008·Hormones and Behavior·Douglas Ashley MonksMichael Quentin Kemp

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