Nature Genetics
21, 434 - 439 (1999)
doi:10.1038/7777
The gene encoding proline dehydrogenase modulates sensorimotor gating
in miceJoseph Gogos1, 2, 5, Miklos Santha1, 5, Zoltan Takacs1, Kevin D Beck3, Victoria Luine3, Louis R Lucas1, J. Victor Nadler4
& Maria Karayiorgou11
The Rockefeller University, New York,
New York 10021, USA. 2
Columbia University, College of Physicians & Surgeons,
Center for Neurobiology & Behavior, New York,
New York 10032, USA. 3
Hunter College, Psychology Department,
New York, New York 10021, USA. 4
Duke University Medical Center, Department of Pharmacology
& Cancer Biology, Durham, North Carolina
27710, USA. 5
These authors contributed equally to this work
Correspondence should be addressed to Maria Karayiorgou karayim@rockvax.rockefeller.eduHemizygous 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.
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