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Letter
Nature Genetics  21, 434 - 439 (1999)
doi:10.1038/7777

The gene encoding proline dehydrogenase modulates sensorimotor gating in mice

Joseph Gogos1, 2, 5, Miklos Santha1, 5, Zoltan Takacs1, Kevin D Beck3, Victoria Luine3, Louis R Lucas1, J. Victor Nadler4 & Maria Karayiorgou1

1  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.edu
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.

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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