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

Z. Katarova, E. Mugnaini, G. Sekerkova, J. R. Mann, A. Aszodi, Z. Bösze, R. Greenspan, G. Szabo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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
Volume10
Issue number3
DOIs
Publication statusPublished - 1998

Fingerprint

5' Flanking Region
Transgenic Mice
Central Nervous System
Galactosidases
GABAergic Neurons
Housekeeping
Glutamate Decarboxylase
Nucleic Acid Regulatory Sequences
Gene Fusion
Transgenes
Genetic Promoter Regions
Epigenomics
Introns
Genes
Escherichia coli
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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. / Katarova, Z.; Mugnaini, E.; Sekerkova, G.; Mann, J. R.; Aszodi, A.; Bösze, Z.; Greenspan, R.; Szabo, G.

In: European Journal of Neuroscience, Vol. 10, No. 3, 1998, p. 989-999.

Research output: Contribution to journalArticle

Katarova, Z. ; Mugnaini, E. ; Sekerkova, G. ; Mann, J. R. ; Aszodi, A. ; Bösze, Z. ; Greenspan, R. ; Szabo, G. / 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. In: European Journal of Neuroscience. 1998 ; Vol. 10, No. 3. pp. 989-999.
@article{098d5ec02df44be69cb1a908f3a90998,
title = "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",
abstract = "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.",
keywords = "Epigenetic regulation, GABA, Gene regulation, Inhibitory neurons, Neuron-restrictive silencers, Spatial enhancers",
author = "Z. Katarova and E. Mugnaini and G. Sekerkova and Mann, {J. R.} and A. Aszodi and Z. B{\"o}sze and R. Greenspan and G. Szabo",
year = "1998",
doi = "10.1046/j.1460-9568.1998.00109.x",
language = "English",
volume = "10",
pages = "989--999",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - 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

AU - Katarova, Z.

AU - Mugnaini, E.

AU - Sekerkova, G.

AU - Mann, J. R.

AU - Aszodi, A.

AU - Bösze, Z.

AU - Greenspan, R.

AU - Szabo, G.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Epigenetic regulation

KW - GABA

KW - Gene regulation

KW - Inhibitory neurons

KW - Neuron-restrictive silencers

KW - Spatial enhancers

UR - http://www.scopus.com/inward/record.url?scp=0031926194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031926194&partnerID=8YFLogxK

U2 - 10.1046/j.1460-9568.1998.00109.x

DO - 10.1046/j.1460-9568.1998.00109.x

M3 - Article

C2 - 9753166

AN - SCOPUS:0031926194

VL - 10

SP - 989

EP - 999

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 3

ER -