TY - JOUR
T1 - Neuronal subtype-specific expression directed by the GABA(A) receptor δ subunit gene promoter/upstream region in transgenic mice and in cultured cells
AU - Luscher, Bernhard
AU - Häuselmann, Remo
AU - Leitgeb, Sabine
AU - Rülicke, Thomas
AU - Fritschy, Jean Marc
N1 - Funding Information:
We are grateful to J.L. Dreyer, U. Otten, W. Rosenthal, C.B. Wollheim for the gift of cell lines, S. Forss-Petter and S. Rusconi for plasmids, C. Essrich for advice on neuronal cultures, G. Reyes for technical assistance, and P. Mitchell and H. Mohler for critical comments on the manuscript. This work was supported by grants from the Swiss National Science Foundation (#30-30115.90, 31-39702.93) to B.L.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/11
Y1 - 1997/11
N2 - The promoter of the GABA(A) receptor δ subunit gene was analyzed in transgenic mice and in cultured cells to study sequences involved in neuronal subtype-specific gene expression. A 6.4-kb genomic fragment faithfully directed neuron-specific transcription of a lacZ reporter gene in the central nervous system. The transgene expression pattern in the cerebral cortex, hippocampal formation, thalamus, and brainstem was consistent with the regional and neuronal subtype-specific expression of the endogenous δ subunit protein in both developing and mature brain. In the cerebellum, however, the transgene was ectopically expressed in Purkinje cells and silent in granule cells, where the endogenous δ subunit is abundantly expressed. These mice provide a useful tool for investigating activity-dependent regulation of GABA(A) receptor expression under physiological and pathological conditions. Transfection studies using primary cortical neurons and astroglial cells revealed that the δ subunit gene promoter was selectively active in neurons even when truncated to a 267-bp core fragment. In conclusion, the δ subunit gene promoter/upstream region contains the information for neuronal subtype-specific expression in the entire brain except in the cerebellum and is selectively active in primary cortical neurons in vitro.
AB - The promoter of the GABA(A) receptor δ subunit gene was analyzed in transgenic mice and in cultured cells to study sequences involved in neuronal subtype-specific gene expression. A 6.4-kb genomic fragment faithfully directed neuron-specific transcription of a lacZ reporter gene in the central nervous system. The transgene expression pattern in the cerebral cortex, hippocampal formation, thalamus, and brainstem was consistent with the regional and neuronal subtype-specific expression of the endogenous δ subunit protein in both developing and mature brain. In the cerebellum, however, the transgene was ectopically expressed in Purkinje cells and silent in granule cells, where the endogenous δ subunit is abundantly expressed. These mice provide a useful tool for investigating activity-dependent regulation of GABA(A) receptor expression under physiological and pathological conditions. Transfection studies using primary cortical neurons and astroglial cells revealed that the δ subunit gene promoter was selectively active in neurons even when truncated to a 267-bp core fragment. In conclusion, the δ subunit gene promoter/upstream region contains the information for neuronal subtype-specific expression in the entire brain except in the cerebellum and is selectively active in primary cortical neurons in vitro.
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U2 - 10.1016/S0169-328X(97)00242-8
DO - 10.1016/S0169-328X(97)00242-8
M3 - Article
C2 - 9427522
AN - SCOPUS:0343632347
SN - 0169-328X
VL - 51
SP - 197
EP - 211
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -