Zn2+ reverses functional deficits in a de novo dopamine transporter variant associated with autism spectrum disorder

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• 作者：Peter J Hamilton (1) (2)
  Aparna Shekar (1) (3)
  Andrea N Belovich (1) (3)
  Nicole Bibus Christianson (1) (2)
  Nicholas G Campbell (1) (2)
  James S Sutcliffe (1) (2)
  Aurelio Galli (1) (2)
  Heinrich JG Matthies (1) (2)
  Kevin Erreger (1) (2)
  
  1. Department of Molecular Physiology and Biophysics ; Vanderbilt University School of Medicine ; Room 7124 MRB III ; 465 21st Avenue S ; Nashville ; TN ; 37232 ; USA
  2. Vanderbilt Brain Institute ; Vanderbilt University School of Medicine ; Nashville ; Tennessee ; USA
  3. Department of Pharmacology ; Vanderbilt University School of Medicine ; Nashville ; Tennessee ; USA
  
• 关键词：Autism spectrum disorder ; Dopamine ; Zinc ; Transporter ; de novo mutation
• 刊名：Molecular Autism
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：6
• 期：1
• 全文大小：429 KB
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• 刊物主题：Neurology; Neurosciences; Neuropsychology; Molecular Medicine; Psychiatry; Pediatrics;
• 出版者：BioMed Central
• ISSN：2040-2392

文摘

Our laboratory recently characterized a novel autism spectrum disorder (ASD)-associated de novo missense mutation in the human dopamine transporter (hDAT) gene SLC6A3 (hDAT T356M). This hDAT variant exhibits dysfunctional forward and reverse transport properties that may contribute to DA dysfunction in ASD. Here, we report that Zn2+ reverses, at least in part, the functional deficits of ASD-associated hDAT variant T356M. These data suggest that the molecular mechanism targeted by Zn2+ to restore partial function in hDAT T356M may be a novel therapeutic target to rescue functional deficits in hDAT variants associated with ASD.