Abnormal anxiety-related behavior in serotonin transporter null mutant mice: The influence of genetic background

A. Holmes, Q. Li, D. L. Murphy, E. Gold, J. N. Crawley

Research output: Contribution to journalArticlepeer-review

257 Scopus citations


Serotonin transporter (5-HTT) null mutant mice provide a model system to study the role genetic variation in the 5-HTT plays in the regulation of emotion. Anxiety-like behaviors were assessed in 5-HTT null mutants with the mutation placed on either a B6 congenic or a 129S6 congenic background. Replicating previous findings, B6 congenic 5-HTT null mutants exhibited increased anxiety-like behavior and reduced exploratory locomotion on the light ↔ dark exploration and elevated plus-maze tests. In contrast, 129S6 congenic 5-HTT null mutant mice showed no phenotypic abnormalities on either test. 5-HTT null mutants on the 129S6 background showed reduced 5-HT 1A receptor binding (as measured by quantitative autoradiography) and reduced 5-HT1A receptor function (as measured by 8-OH-DPAT-indcued hypothermia). These data confirm that the 5-HTT null mutation produced alterations in brain 5-HT function in mice on the 129S6 background, thereby discounting the possibility that the absence of an abnormal anxiety-like phenotype in these mice was due to a suppression of the mutation by 129 modifier genes. Anxiety-like behaviors in the light ↔ dark exploration and elevated plusmaze tests were significantly higher in 129S6 congenic +/+ mice as compared to B6 congenic +/+ mice. This suggests that high baseline anxiety-like behavior in the 129S6 strain might have precluded detection of the anxiety-like effects of the 5-HTT null mutation on this background. Present findings provide further evidence linking genetic variation in the 5-HTT to abnormalities in mood and anxiety. Furthermore, these data highlight the utility of conducting behavioral phenotyping of mutant mice on multiple genetic backgrounds.

Original languageEnglish (US)
Pages (from-to)365-380
Number of pages16
JournalGenes, Brain and Behavior
Issue number6
StatePublished - 2003
Externally publishedYes


  • 5-HT receptor
  • Anxiety
  • Gene
  • Genetic background
  • Inbred strains
  • Mouse
  • Serotonin
  • Serotonin transporter

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience


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