Regulation of cell-type specific expression of lacZ by the 5′-flanking region of mouse GAD67 gene in the central nervous system of transgenic mice

Zoya Katarova, Enrico Mugnaini, Gabriela Sekerková, Jeffrey R. Mann, Attila Aszódi, Zsuzsanna Bösze, Ralph Greenspan, Gábor Szabó

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The transcriptional regulation of the murine gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was studied by β-galactosidase histochemistry in transgenic mice carrying fusion genes between progressively longer portions of the 5′-upstream regulatory region of GAD67 and E. coli lacZ. No expression was detected in brains of mice carrying 1.3 kb of upstream sequences including a housekeeping and two conventional promoters, and two negative regulatory elements with homology to known silencers. In mice carrying the same portion of the promoter region plus the first intron, lacZ expression in the adult central nervous system was found in few, exclusively neuronal sites. The number of correctly stained GABAergic centres increased dramatically with increasing the length of the 5′-upstream region included in the construct which suggests that multiple putative spatial enhancers are located in this region. Their action is influenced by epigenetic mechanisms that may be due to site-of-integration and transgene copy-number effects. Additional cis-acting elements are needed to obtain fully correct expression in all GABAergic neurons of the adult central nervous system.

Original languageEnglish
Pages (from-to)989-999
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number3
Publication statusPublished - 1 Jan 1998
Externally publishedYes


  • Epigenetic regulation
  • GABA
  • Gene regulation
  • Inhibitory neurons
  • Neuron-restrictive silencers
  • Spatial enhancers

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