The gene encoding proline dehydrogenase modulates sensorimotor gating in mice

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have be en associated with a number of psychiatric and behavioural phenotypes, incl uding schizophrenial(1-3). Here we report the isolation and characterizatio n of PRODH, a human homologue of Drosophila melanogaster sluggish-A (sIgA), which encodes proline dehydrogenase responsible for the behavioural phenot ype of the sIgA mutant(4). PRODH is localized at chromosome 22q11 in a regi on deleted in some psychiatric patients. We also isolated the mouse homolog ue of sIgA (Prodh), identified a mutation in this gene in the Pro/Re hyperp rolinaemic mouse strain and found that these mice have a deficit in sensori motor gating accompanied by regional neurochemical alterations in the brain . Sensorimotor gating is a neural filtering process that allows attention t o be focused on a given stimulus, and is affected in patients with neuropsy chiatric 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 PR ODH, suggest a potential involvement of this gene in the 22q11-associated p sychiatric and behavioural phenotypes.