title: Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome.
abstract: Fragile X Syndrome (FXS) is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT) suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS.
authors.affiliation: Department of Zoology, University of Oklahoma, Norman, Oklahoma, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Tauber
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Vanlandingham
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000209:etiology / Q000503:physiopathology*; D006120:Grooming; D009770:Obsessive Behavior / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D050493:Vesicular Monoamine Transport Proteins; C467328:FMR1 protein, Drosophila
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7746-50
references.pmid: 12032354
references.citation: Am J Med Genet. 1992 Apr 15-May 1;43(1-2):35-46
references.pmid: 1605210
references.citation: Neuron. 2007 Dec 20;56(6):955-62
references.pmid: 18093519
references.citation: Neuron. 2008 Aug 28;59(4):634-47
references.pmid: 18760699
references.citation: Cell. 2001 Nov 16;107(4):477-87
references.pmid: 11719188
references.citation: Behav Neurosci. 2008 Apr;122(2):293-300
references.pmid: 18410169
references.citation: PLoS One. 2011 Feb 22;6(2):e17073
references.pmid: 21364941
references.citation: J Neurosci. 2008 Oct 8;28(41):10200-5
references.pmid: 18842880
references.citation: Neuron. 2003 Feb 6;37(3):417-31
references.pmid: 12575950
references.citation: J Neurosci. 2010 Jan 13;30(2):694-702
references.pmid: 20071534
references.citation: J Neurosci. 2005 Oct 12;25(41):9460-9
references.pmid: 16221856
references.citation: Curr Biol. 2004 Jun 22;14(12):1025-34
references.pmid: 15202995
references.citation: Nat Chem Biol. 2008 Apr;4(4):256-63
references.pmid: 18327252
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5401-4
references.pmid: 9144249
references.citation: Am J Med Genet. 1999 May 28;84(3):268-71
references.pmid: 10331605
references.citation: Am J Med Genet C Semin Med Genet. 2010 Nov 15;154C(4):469-76
references.pmid: 20981777
references.citation: Behav Neurosci. 2006 Dec;120(6):1367-79
references.pmid: 17201482
references.citation: Am J Ment Retard. 2008 Jan;113(1):44-53
references.pmid: 18173299
references.citation: Curr Biol. 2002 Aug 6;12(15):1331-5
references.pmid: 12176363
references.citation: Mol Cell Biol. 2000 Nov;20(22):8536-47
references.pmid: 11046149
references.citation: Science. 1994 Jun 17;264(5166):1702-14
references.pmid: 8209251
references.citation: Cell. 2001 Nov 30;107(5):591-603
references.pmid: 11733059
references.citation: Brain Res. 2011 Mar 22;1380:106-19
references.pmid: 21078304
references.citation: J Neurodev Disord. 2011 Mar;3(1):57-67
references.pmid: 21475730
references.citation: J Autism Dev Disord. 2009 Apr;39(4):572-88
references.pmid: 19037716
references.citation: J Neurosci. 2009 Feb 18;29(7):1948-61
references.pmid: 19228950
references.citation: Neuron. 2002 Jun 13;34(6):973-84
references.pmid: 12086644
references.citation: Neuron. 2008 Oct 23;60(2):201-14
references.pmid: 18957214
references.citation: J Neurosci. 2010 May 26;30(21):7121-3
references.pmid: 20505079
references.citation: Development. 2008 Aug;135(15):2637-48
references.pmid: 18579676
references.citation: Am J Med Genet. 1996 Aug 9;64(2):350-5
references.pmid: 8844079
references.citation: J Child Neurol. 2011 Aug;26(8):940-8
references.pmid: 21527394
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4131-6
references.pmid: 9108117
references.citation: Am J Ment Retard. 2008 Nov;113(6):427-38
references.pmid: 19127654
references.citation: J Neurosci. 2004 Jun 23;24(25):5798-809
references.pmid: 15215302
references.citation: Am J Med Genet A. 2004 Sep 1;129A(3):225-34
references.pmid: 15326621
references.citation: Dev Neurobiol. 2007 May;67(6):778-91
references.pmid: 17443824
references.citation: Curr Biol. 2004 Oct 26;14(20):1863-70
references.pmid: 15498496
references.citation: Am J Med Genet. 1989 Aug;33(4):513-8
references.pmid: 2596514
references.citation: Development. 2008 Apr;135(8):1547-57
references.pmid: 18321984
references.citation: Biogerontology. 2010 Jun;11(3):347-62
references.pmid: 20039205
references.citation: Mol Psychiatry. 2006 Jan;11(1):99-113
references.pmid: 16189511
references.citation: J Neurophysiol. 2009 Feb;101(2):672-87
references.pmid: 19036865
references.citation: Eur J Hum Genet. 2008 Jun;16(6):666-72
references.pmid: 18398441
references.citation: Mol Autism. 2010 Sep 21;1(1):12
references.pmid: 20858229
references.citation: J Mol Neurosci. 2012 Feb;46(2):272-5
references.pmid: 21547530
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Am J Hum Genet. 2009 Oct;85(4):503-14
references.pmid: 19804849
references.citation: Am J Med Genet A. 2005 Jun 1;135(2):155-60
references.pmid: 15880753
references.citation: Neuropharmacology. 2005 Dec;49(7):1053-66
references.pmid: 16054174
references.citation: Neuron. 2002 Jun 13;34(6):961-72
references.pmid: 12086643
references.citation: J Neurobiol. 2005 Sep 5;64(3):239-58
references.pmid: 15849736
references.citation: Mol Cell Proteomics. 2005 Mar;4(3):278-90
references.pmid: 15634690
references.citation: Neuron. 2005 Mar 3;45(5):753-64
references.pmid: 15748850
references.citation: Cell. 1991 May 31;65(5):905-14
references.pmid: 1710175
references.citation: Nat Neurosci. 2008 Oct;11(10):1143-5
references.pmid: 18776892
references.citation: Proc Natl Acad Sci U S A. 1979 Jul;76(7):3430-4
references.pmid: 16592682
references.citation: Mol Cell Neurosci. 2008 Apr;37(4):747-60
references.pmid: 18280750
references.citation: Am J Med Genet A. 2006 Sep 1;140A(17):1804-13
references.pmid: 16700053