Hemizygous cryptic deletions of the q11 band of human chromosome 22 have
been associated with a number of psychiatric and behavioural phenotypes, including
schizophrenia1,
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 mutant4. 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 disorders5. 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.
