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Cloning and characterization of SDF-1γ, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system

Authors

  • Marc Gleichmann,

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
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    • *

      Current address: Department of Neurology, School of Medicine, University of Tübingen, D-72076 Tübingen

      Current address: †Department Molecular Pharmacology, Grünenthal GmbH, D-52078 Aachen, Germany

  • Clemens Gillen,

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
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      Current address: Department of Neurology, School of Medicine, University of Tübingen, D-72076 Tübingen

      Current address: †Department Molecular Pharmacology, Grünenthal GmbH, D-52078 Aachen, Germany

  • Margarete Czardybon,

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
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  • Frank Bosse,

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
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  • Regine Greiner-Petter,

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
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  • Johannes Auer,

    1. Roche Diagnostics GmbH, Pharma Research, Nonnenwald 2, D-82372, Germany
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  • Hans Werner Müller

    1. Molecular Neurobiology Laboratory, Department of Neurology, and
    2. Biomedical Research Center, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany
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: Dr H.W. Müller, as 1above.
E-mail: mueller@neurologie.uni-duesseldorf.de

Abstract

The cytokines SDF-1α and -1β are two alternatively spliced variants of the CXC (α) chemokines that are highly conserved among species. SDF-1α was shown to function as a B-cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic HIV-1 strains and inducing cell death in human neuronal cell lines. In this report the cloning of the rat SDF-1β cDNA and a new SDF-1 isoform, SDF-1γ, are presented. Using Northern blot analysis, the expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF-1β- and SDF-1γ-mRNA expression is inversely regulated. Whilst SDF-1β-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1γ-mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF-1β-mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF-1β and SDF-1γ mRNAs in the nervous system. Computer-assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides.

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