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Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.

Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.

Pubmed ID: 12506198


  • Ozeki Y
  • Tomoda T
  • Kleiderlein J
  • Kamiya A
  • Bord L
  • Fujii K
  • Okawa M
  • Yamada N
  • Hatten ME
  • Snyder SH
  • Ross CA
  • Sawa A


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

January 7, 2003

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA-00074
  • Agency: NINDS NIH HHS, Id: NS-34172

Mesh Terms

  • Animals
  • Cloning, Molecular
  • Cysteine Endopeptidases
  • DNA Primers
  • Humans
  • Nerve Tissue Proteins
  • Neurites
  • Protein Binding
  • Rats
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion
  • Serine Endopeptidases
  • Subcellular Fractions