Directing gene expression to cerebellar granule cells using γ-aminobutyric acid type A receptor α6 subunit transgenes

August 19, 1997
94 (17) 9417-9421

Abstract

Expression of the γ-aminobutyric acid type A receptor α6 subunit gene is restricted to differentiated granule cells of the cerebellum and cochlear nucleus. The mechanisms underlying this limited expression are unknown. Here we have characterized the expression of a series of α6-based transgenes in adult mouse brain. A DNA fragment containing a 1-kb portion upstream of the start site(s), together with exons 1–8, can direct high-level cerebellar granule cell-specific reporter gene expression. Thus powerful granule cell-specific determinants reside within the 5′ half of the α6 subunit gene body. This intron-containing transgene appears to lack the cochlear nucleus regulatory elements. It therefore provides a cassette to deliver gene products solely to adult cerebellar granule cells.

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Acknowledgments

We thank R. Palmiter for the pnLacF vector, A. Lenton for help with figure preparation, and H. Bading, M. Goedert, A. L. Grant, S. P. Hunt, and S. Munro for discussion. G. King, T. Langford, I. Lavenir, and T. Rabbitts provided invaluable support with transgenic mice. S.B. holds a European Community Training and Mobility of Researchers Fellowship (category 20).

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Information & Authors

Information

Published in

The cover image for PNAS Vol.94; No.17
Proceedings of the National Academy of Sciences
Vol. 94 | No. 17
August 19, 1997
PubMed: 9256497

Classifications

Submission history

Received: April 23, 1997
Accepted: June 6, 1997
Published online: August 19, 1997
Published in issue: August 19, 1997

Acknowledgments

We thank R. Palmiter for the pnLacF vector, A. Lenton for help with figure preparation, and H. Bading, M. Goedert, A. L. Grant, S. P. Hunt, and S. Munro for discussion. G. King, T. Langford, I. Lavenir, and T. Rabbitts provided invaluable support with transgenic mice. S.B. holds a European Community Training and Mobility of Researchers Fellowship (category 20).

Authors

Affiliations

Sabine Bahn
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom
Alison Jones
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom
William Wisden*
Medical Research Council Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom

Notes

*
To whom reprint requests should be addressed. e-mail: [email protected].
Communicated by Erminio Costa, University of Illinois, Chicago, IL

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    Directing gene expression to cerebellar granule cells using γ-aminobutyric acid type A receptor α6 subunit transgenes
    Proceedings of the National Academy of Sciences
    • Vol. 94
    • No. 17
    • pp. 8923-9511

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