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 1 , 2 , 3 . 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 4 . 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 5 . 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.