Human Genetics

, Volume 103, Issue 4, pp 386–392

Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: alternative splicing of mRNA transcripts, genomic structure and sequence

  • Michel Guipponi
  • Hamish S. Scott
  • Jun Kudoh
  • Kazuhiko Kawasaki
  • Kazunori Shibuya
  • A. Shintani
  • Shuichi Asakawa
  • Haiming Chen
  • Maria D. Lalioti
  • Colette Rossier
  • Shinsei Minoshima
  • Nobuyoshi Shimizu
  • Stylianos E. Antonarakis
Rapid communication

DOI: 10.1007/s004390050838

Cite this article as:
Guipponi, M., Scott, H., Kudoh, J. et al. Hum Genet (1998) 103: 386. doi:10.1007/s004390050838

Abstract

Cyclic nucleotide-specific phosphodiesterases (PDEs) play an essential role in signal transduction by regulating the intracellular concentration of second messengers (cAMP and cGMP). We have identified and made an initial characterization of a full-length cDNA encoding a novel human cyclic nucleotide phosphodiesterase, PDE9A. At least four different mRNA transcripts (PDE9A1, A2, A3, A4) are produced as a result of alternative splicing of 5′ exons, potentially changing the N-terminal amino acid sequences of the encoded proteins. All these predicted proteins would contain a 3′,5′-cyclic nucleotide phosphodiesterase signature motif (Prosite no. PDOC00116). Northern blot analysis revealed several mRNA species of approximately 2.4 kb with varying expression patterns and intensities in most tissues examined, except blood. We have also isolated the mouse homolog of the human PDE9A2 mRNA transcript, pde9A2. The human and mouse isoforms have 93 and 83% sequence identity at the amino acid and nucleotide levels, respectively. PDE9A was mapped to 21q22.3, between TFF1 and D21S360. Comparison of the PDE9A1 cDNA with the genomic sequence from the region revealed that the gene is split into 20 exons that extend over 122 kb. Comparison of the physical map of the region and the genomic sequence further refines the mapping, with D21S113 being derived from intron 15. Several genetic disorders map to 21q22.3, including one form of bipolar affective disorder. Since functional disturbances in intraneuronal signal transmission via second messengers play an important role in the pathophysiology of affective disorders, PDE9A is a strong candidate for such a role by position and function.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Michel Guipponi
    • 1
  • Hamish S. Scott
    • 1
  • Jun Kudoh
    • 3
  • Kazuhiko Kawasaki
    • 3
  • Kazunori Shibuya
    • 3
  • A. Shintani
    • 3
  • Shuichi Asakawa
    • 3
  • Haiming Chen
    • 1
  • Maria D. Lalioti
    • 1
  • Colette Rossier
    • 1
  • Shinsei Minoshima
    • 3
  • Nobuyoshi Shimizu
    • 3
  • Stylianos E. Antonarakis
    • 1
  1. 1.Laboratory of Human Molecular Genetics, Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital of Geneva, CH-1211 Geneva 4, SwitzerlandCH
  2. 2.Division of Medical Genetics, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland e-mail: Stylianos.Antonarakis@medecine.unige.ch, Tel.: +41-22-702-57-08, Fax: +41-22-702-57-06CH
  3. 3.Department of Molecular Biology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, JapanJP