Book chapter
The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction
Monoamine Transporters, pp.235-270
Advances in neurobiology, v. 46, Springer
2025
DOI: 10.1007/978-3-031-96364-3_10
PMID: 41051713
Abstract
The clinical efficacy of psychostimulant drugs, which target monoamine transporters, in treating attention-deficit/hyperactivity disorders (ADHDs) has stimulated interest on the role of transporter proteins like the dopamine (DA) transporter (DAT) in neurotransmission as well as the potential utility of DAT knockout organisms as models for neuropsychiatric disorders. Indeed, the study of DAT-deficient worms, flies, fish, mice, and rats has revealed a conserved role for DAT in the control of motor behavior as well as repetitive behavior, threat aversion, social behavior, and cognition in mammals. However, the disconnect between phenotypes observed in DAT-deficient model organisms and humans, which exhibit an early-onset syndrome characterized by Parkinsonism/dystonia and premature death, challenges the construct validity of DAT knockout models with respect to modeling neurobehavioral disorders. As an alternate approach, several groups have utilized coding variants in the SLC6A3 gene linked to psychiatric conditions, which display divergent molecular phenotypes. This chapter reviews the development and characterization of models of DAT gene deletion and mutation with a particular emphasis on comparing/contrasting the functional impact of DAT deficiency to DAT dysregulation triggered by neuropsychiatric disorder-linked DAT mutants in vivo. Ultimately, the study of DAT knockout and mutant models has revealed novel functions for DA in the mammalian brain, uncovered a dynamic interplay between the monoaminergic systems, highlighted sex differences in the DA system that determine the behavioral trajectory of DAT deregulation, and allowed for the screening of potential leads for therapeutics to treat disorders linked to aberrant dopaminergic neurotransmission.
Details
- Title: Subtitle
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction
- Creators
- Adele Stewart - University of IowaRandy D Blakely - Florida Atlantic University
- Resource Type
- Book chapter
- Publication Details
- Monoamine Transporters, pp.235-270
- Series
- Advances in neurobiology; v. 46
- DOI
- 10.1007/978-3-031-96364-3_10
- PMID
- 41051713
- eISBN
- 9783031963643; 3031963644
- ISSN
- 2190-5215
- eISSN
- 2190-5223
- Publisher
- Springer; Cham
- Language
- English
- Date published
- 2025
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984969240302771
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