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 RIS Download
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