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  • Original Research Article
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A dopamine transporter mutation associated with bipolar affective disorder causes inhibition of transporter cell surface expression

Molecular Psychiatry volume 10, pages 1104–1109 (2005)Cite this article

A Corrigendum to this article was published on 27 June 2006

Abstract

The dopamine transporter (DAT) plays a crucial role in dopaminergic neurotransmission as it clears the extracellular space of dopamine (DA) and thus controls the concentration of active neurotransmitter. Genetic association studies have reported a variable number of tandem repeat polymorphisms in the 3′-noncoding region of the DAT gene implicating this protein in the development of various psychiatric disorders. In a sample of bipolar patients, two rare missense substitutions (A559V and E602G) have been identified, one of which (E602G) was inherited by the patient from her affected father. None of these mutations had been identified in any control subjects of this survey. Using a heterologous cellular expression system, we have analysed possible consequences of these mutations on functional properties of the encoded DAT protein. DA transport measurements and antagonist binding revealed that the A559V mutant protein is fully functional, whereas the E602G mutant is not. Further analyses by confocal microscopy showed that the E602G protein is transcribed and translated but not delivered to the cell surface. Taken together, our results suggest that this missense mutation has functional consequences thus supporting the need to screen larger samples of patients and their relatives for this rare but bipolar disorder-associated mutation in the DAT gene.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (SCHL353/4-2 to PS and SFB636 to MR and PS). We thank Helene Schamber for excellent technical assistance.

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Authors and Affiliations

  1. Biochemical Laboratory, Central Institute of Mental Health, Mannheim, Germany

    S Horschitz, R Hummerich, T Lau & P Schloss

  2. Department of Genetic Epidemiology, Central Institute of Mental Health, Mannheim, Germany

    M Rietschel

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  1. S Horschitz
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  2. R Hummerich
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Correspondence to P Schloss.

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Horschitz, S., Hummerich, R., Lau, T. et al. A dopamine transporter mutation associated with bipolar affective disorder causes inhibition of transporter cell surface expression. Mol Psychiatry 10, 1104–1109 (2005). https://doi.org/10.1038/sj.mp.4001730

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