Overexpression of γ-aminobutyric acid transporter subtype I leads to cognitive deterioration in transgenic mice

Y. H. Ma, X. G. Zhou, S. H. Duan, J. H. Hu, B. F. Lu, Y. Yu, Z. T. Mei, J. Fei, L. H. Guo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


AIM: To explore the physiological role of γ-aminobutyric acid transporter subtype I (GAT1) in cognition. METHODS: Transgenic mice were produced by pronuclei microinjection method. Integration of transgene was identified by Southern-blot and PCR analysis in various generations. Level of GAT1 mRNA in a variety of tissues was evaluated by semi-quantitative RT-PCR analysis. GAT1 protein was detected by immunofluorescence and histochemistry analysis. Associative learning capacity was analyzed by conditioned avoidance task. Memory retention was assessed by novel object recognition test. Morphology of synaptosomes was examined by electron microscope. RESULTS: Four independent founder mice bearing various copies of transgene were generated. GAT1 was evidently overexpressed at both mRNA and protein level in a variety of tissues from transgenic mice. In comparision with wild-type mice, transgenic mice exhibited significantly declined associative learning capacity (P < 0.01) and decreased memory retention (P < 0.01 in 1-h-retention, and P < 0.05 in 1-d-retention). In addition, the amount of asymmetric synapses in the brain of transgenic mice was reduced approximately by 24 %, relative to wild-type mice. CONCLUSION: Overexpression of GAT1 in mice results in cognitive deterioration, indicating that the alteration in the expression of γ-aminobutyric acid transporters is involved in the pathophysiological mechanism underlying some cognitive deficiencies.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalActa Pharmacologica Sinica
Issue number4
StatePublished - 2001
Externally publishedYes


  • Cartier proteins
  • Cognition
  • Gene expression
  • Learning
  • Memory
  • Synapses
  • Transgenic mice

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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