Genetic perspectives on the serotonin transporter

Dennis L. Murphy, Qian Li, Sharon Engel, Christine Wichems, Anne Andrews, Klaus Peter Lesch, George Uhl

Research output: Contribution to journalArticle

Abstract

The serotonin transporter (5-HTT) is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuropsychiatric and related disorders. The discovery that the gene that expresses the 5-HTT possesses a functional promoter-region polymorphism, which is associated with temperament and personality traits such as anxiety and negative emotionality as well as some behaviors, led to many studies examining this polymorphism in individuals with different neuropsychiatric disorders. The subsequent development of mice with a targeted disruption of the 5-HTT in our laboratory has provided an experimental model to examine the many consequences of diminished (in +/-, heterozygote mice) or absent (in -/-, homozygote knockout mice) function of the 5-HTT. The 5-HTT-deficient mice were also crossed with other knockout mice, allowing the study of multiple neurobiologic dysfunctions. As multiple genes are probably involved in the expression of complex behaviors such as anxiety, as well as neuropsychiatric disorders, these more genetically complex mice may more closely model disorders with complex etiologies. Thus, the combination of these comparative human and mouse studies may extend the opportunities to examine genetic alterations from a novel "bottom-up" approach [gene knockout or partial gene knockout in a combinational gene × gene × (yet unknown) gene approach], which is complementary to the traditional "top-down" genetic approach based upon studies of individuals with diagnosed neuropsychiatric disorders and their family members.

Original languageEnglish (US)
Pages (from-to)487-494
Number of pages8
JournalBrain Research Bulletin
Volume56
Issue number5
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Gene Knockout Techniques
Knockout Mice
Genes
Anxiety
Temperament
Serotonin Uptake Inhibitors
Homozygote
Genetic Association Studies
Heterozygote
Genetic Promoter Regions
Antidepressive Agents
Personality
Theoretical Models

Keywords

  • Neuropsychiatric disorders
  • Personality
  • Polymorphisms
  • Serotonin
  • Transgenic (knockout/mutant) mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Murphy, D. L., Li, Q., Engel, S., Wichems, C., Andrews, A., Lesch, K. P., & Uhl, G. (2001). Genetic perspectives on the serotonin transporter. Brain Research Bulletin, 56(5), 487-494. https://doi.org/10.1016/S0361-9230(01)00622-0

Genetic perspectives on the serotonin transporter. / Murphy, Dennis L.; Li, Qian; Engel, Sharon; Wichems, Christine; Andrews, Anne; Lesch, Klaus Peter; Uhl, George.

In: Brain Research Bulletin, Vol. 56, No. 5, 15.11.2001, p. 487-494.

Research output: Contribution to journalArticle

Murphy, DL, Li, Q, Engel, S, Wichems, C, Andrews, A, Lesch, KP & Uhl, G 2001, 'Genetic perspectives on the serotonin transporter', Brain Research Bulletin, vol. 56, no. 5, pp. 487-494. https://doi.org/10.1016/S0361-9230(01)00622-0
Murphy DL, Li Q, Engel S, Wichems C, Andrews A, Lesch KP et al. Genetic perspectives on the serotonin transporter. Brain Research Bulletin. 2001 Nov 15;56(5):487-494. https://doi.org/10.1016/S0361-9230(01)00622-0
Murphy, Dennis L. ; Li, Qian ; Engel, Sharon ; Wichems, Christine ; Andrews, Anne ; Lesch, Klaus Peter ; Uhl, George. / Genetic perspectives on the serotonin transporter. In: Brain Research Bulletin. 2001 ; Vol. 56, No. 5. pp. 487-494.
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