New Species of Human Tyrosine Hydroxylase mRNA Are Produced in Variable Amounts in Adrenal Medulla and Are Overexpressed in Progressive Supranuclear Palsy

Authors

  • Sylvie Dumas,

    1. Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 9923;
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    • Drs. S. Dumas and H. Le Hir contributed equally to this study.

  • Hervé Le Hir,

    1. Centre de Génétique Moléculaire, Laboratoire associéà l'Université Pierre et Marie Curie, CNRS, Gif sur Yvette, France
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    • Drs. S. Dumas and H. Le Hir contributed equally to this study.

  • Sylvie Bodeau-Péan,

    1. Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 9923;
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  • Etienne Hirsch,

    1. INSERM U289, Hôpital de la Salpêtrière, Paris; and
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  • Claude Thermes,

    1. Centre de Génétique Moléculaire, Laboratoire associéà l'Université Pierre et Marie Curie, CNRS, Gif sur Yvette, France
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  • Jacques Mallet

    Corresponding author
    1. Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 9923;
      Address correspondence and reprint requests to Dr. J. Mallet at Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 9923, Batiment CERVI, Hôpital de la Salpêtrière, 75013 Paris, France.
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Address correspondence and reprint requests to Dr. J. Mallet at Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, CNRS UMR 9923, Batiment CERVI, Hôpital de la Salpêtrière, 75013 Paris, France.

Abstract

Abstract: Alternative splicing of human tyrosine hydroxylase (TH) pre-mRNA produces four mRNAs leading to four different TH isoforms and is thought to have important regulatory functions. We show that the diversity of TH mRNAs is greater than previously described in the autonomous nervous system: New splice junctions corresponding to the skipping of exon 3 were identified by amplification of cDNA synthesized from pheochromocytoma RNA. In all cases the reading frame was maintained. These species were assayed by RNase protection experiments; their abundance (4–6%) was comparable to that of the previously identified human TH-3 and -4 species in normal adrenal medulla. However, higher levels (11–34%) of these species were found in adrenal medullas of patients suffering from progressive supranuclear palsy. Whether such changes are specific to the disease or the consequences of the stress associated with this severe neurodegeneration remains to be established.

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