Structure of the mouse glutamate decarboxylase 65 gene and its promoter: Preferential expression of its promoter in the GABAergic neurons of transgenic mice

Kimitoshi Makinae, Takashi Kobayashi, Takayasu Kobayashi, Hideichi Shinkawa, Hiroyuki Sakagami, Hisatake Kondo, Fumi Tashiro, Jun Ichi Miyazaki, Kunihiko Obata, Shinri Tamura, Yuchio Yanagawa

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

GABA is synthesized by glutamate decarboxylase (GAD), which has two forms, GAD65 and GAD67. To elucidate the molecular mechanisms of mouse GAD65 (mGAD65) gene expression, we isolated and characterized the mGAD65 gene. The mGAD65 gene was found to be divided into 16 exons and spread over 75 kb. The sequence of the first exon and the 5'-flanking region indicated the presence of potential neuron-specific cisregulatory elements. We used transgenic mice to examine the expression pattern conferred by a 9.2-kb promoter-proximal DNA fragment of the mGAD65 gene fused to the bacterial lacZ reporter gene. Transgenic mice showed high β-galactosidase activity specifically in brain and testis. They also showed characteristic patterns of transgene expression in olfactory bulb, cerebellar cortex, and spinal cord, a similar expression pattern to that of endogenous mGAD65. However, no transgene expression was observed in the ventral thalamus or hypothalamus, in which high mGAD65 gene expression levels have been observed. These results suggest that the 9.2-kb DNA fragment of the mGAD65 gene is associated with its tissue-specific expression and its targeted expression in GABAergic neurons of specific brain regions but that additional regulatory elements are necessary to obtain fully correct expression.

Original languageEnglish
Pages (from-to)1429-1437
Number of pages9
JournalJournal of Neurochemistry
Volume75
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • GABAergic neuron
  • Gene structure
  • Glutamate decarboxylase 65
  • Promoter
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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