The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons

被引:141
作者
Michelhaugh, SK
Fiskerstrand, C
Lovejoy, E
Bannon, MJ
Quinn, JP
机构
[1] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA
[2] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48202 USA
[3] Univ Edinburgh, Dept Vet Pathol, Edinburgh EH9 1QH, Midlothian, Scotland
[4] Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England
[5] Univ Liverpool, Dept Human Anat & Cell Biol, Liverpool L69 3BX, Merseyside, England
关键词
VNTR; biolistic transfection; organotypic slice culture; GFP; gene expression;
D O I
10.1046/j.1471-4159.2001.00647.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The dopamine (DAT) and serotonin (SERT) transporter genes both contain variable number of tandem repeats (VNTR) in non-coding gene regions which have been correlated with a predisposition to a variety of CNS disorders. There is considerable homology between individual DAT and SERT repeat DNA sequences, which is reflected in their ability to compete with each other for specific protein binding as demonstrated by electrophoretic mobility shift assay. The SERT VNTR has recently been shown to act as a transcriptional enhancer. Because of the similarities between SERT and DAT VNTRs, the DAT VNTR may also enhance transcription. This study demonstrates by lipid transfection into an immortalized dopaminergic cell line and biolistic transfection into dopamine neurons in neonatal rat midbrain slices that the human nine-repeat DAT VNTR can enhance transcription. This enhancing activity suggests that the DAT VNTR may play a role in regulation of DAT gene expression. Keywords: VNTR, biolistic transfection, organotypic slice culture, GFP, gene expression.
引用
收藏
页码:1033 / 1038
页数:6
相关论文
共 20 条
[1]   Neurotransmitter transporters as molecular targets for addictive drugs [J].
Amara, SG ;
Sonders, MS .
DRUG AND ALCOHOL DEPENDENCE, 1998, 51 (1-2) :87-96
[2]  
Bannon M. J., 1998, PSYCHOPHARMACOLOGY 4
[3]   Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder [J].
Barr, CL ;
Xu, C ;
Kroft, J ;
Feng, Y ;
Wigg, K ;
Zai, G ;
Tannock, R ;
Schachar, R ;
Malone, M ;
Roberts, W ;
Nöthen, MM ;
Grünhage, F ;
Vandenbergh, DJ ;
Uhl, G ;
Sunohara, G ;
King, N ;
Kennedy, JL .
BIOLOGICAL PSYCHIATRY, 2001, 49 (04) :333-339
[4]   Structure of a variable number tandem repeat of the serotonin transporter gene and association with affective disorder [J].
Battersby, S ;
Ogilvie, AD ;
Smith, CAD ;
Blackwood, DHR ;
Muir, WJ ;
Quinn, JP ;
Fink, G ;
Goodwin, GM ;
Harmar, AJ .
PSYCHIATRIC GENETICS, 1996, 6 (04) :177-181
[5]   An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells [J].
Fiskerstrand, CE ;
Lovejoy, EA ;
Quinn, JP .
FEBS LETTERS, 1999, 458 (02) :171-174
[6]  
GIROS B, 1992, MOL PHARMACOL, V42, P383
[7]   Genotype influences in vivo dopamine transporter availability in human striatum [J].
Heinz, A ;
Goldman, D ;
Jones, DW ;
Palmour, R ;
Hommer, D ;
Gorey, JG ;
Lee, KS ;
Linnoila, M ;
Winberger, DR .
NEUROPSYCHOPHARMACOLOGY, 2000, 22 (02) :133-139
[8]   Prediction of dopamine transporter binding availability by genotype: A preliminary report [J].
Jacobsen, LK ;
Staley, JK ;
Zoghbi, S ;
Seibyl, JP ;
Kosten, TR ;
Innis, RB ;
Gelernter, J .
AMERICAN JOURNAL OF PSYCHIATRY, 2000, 157 (10) :1700-1703
[9]   ORGANIZATION OF THE HUMAN SEROTONIN TRANSPORTER GENE [J].
LESCH, KP ;
BALLING, U ;
GROSS, J ;
STRAUSS, K ;
WOLOZIN, BL ;
MURPHY, DL ;
RIEDERER, P .
JOURNAL OF NEURAL TRANSMISSION-GENERAL SECTION, 1994, 95 (02) :157-162
[10]   A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo [J].
MacKenzie, A ;
Quinn, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15251-15255