A polymorphic glucocorticoid receptor in a mouse population may explain inherited altered stress response and increased anxiety-type behaviors

Dongsheng Xu, Angela Buehner, Jianping Xu, Travis Lambert, Casey Nekl, Merlyn K. Nielsen, You Zhou

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A polymorphic glucocorticoid receptor (GRQn) with an expanded CAG track and two silent mutations, when compared with the sequence of other isoform (GRwt), is found in two outbred mouse lines that were produced by selection for high (SH) or low (SL) stress response from high or low heat loss lines of mice, respectively. The GRQn allele, which is also found in 5 of 16 commonly used inbred mouse lines, had a much higher frequency in SL mice; the GRwt/wt was found only in the SH line. Both GRQn/Qn and GRwt/Qn mice had a much weaker corticosterone response to stress than the GRwt/wt mice. Assessment of open field activity revealed that GRQn/Qn and GRwt/Qn mice exhibited significantly lower velocity and locomotor activity, less time in the center, and much longer duration in corner zones than the GRwt/wt mice. The increased anxiety-type behaviors of the GRQn/Qn and GR wt/Qn mice were confirmed by the "elevated plus maze" test in which GRQn/Qn and GRwt/Qn mice spent significantly less time in the "open arm" and longer duration in the "closed arm," than GRwt/wt mice. These results suggest this GR polymorphism plays a role in complex mechanisms leading to lower corticosterone response to stress, and may also be associated with decreased locomotive and increased anxiety-type behaviors in mice.

Original languageEnglish (US)
Pages (from-to)E1802-E1810
JournalFASEB Journal
Issue number13
StatePublished - Nov 1 2006



  • Corticosterone response
  • Elevated plus maze
  • Mouse model
  • Open field assessment
  • Polyglutamine track

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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