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The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes.

Pubmed ID: 10192398


  • Gogos JA
  • Santha M
  • Takacs Z
  • Beck KD
  • Luine V
  • Lucas LR
  • Nadler JV
  • Karayiorgou M


Nature genetics

Publication Data

April 26, 1999

Associated Grants


Mesh Terms

  • Acoustic Stimulation
  • Amino Acid Metabolism, Inborn Errors
  • Amino Acid Sequence
  • Animals
  • Behavior, Animal
  • Blotting, Northern
  • Brain
  • Chromosomes, Human, Pair 22
  • Female
  • Humans
  • Insect Proteins
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation
  • Neurotransmitter Agents
  • Proline
  • Proline Oxidase
  • Reflex, Startle
  • Sequence Homology, Amino Acid