Behavioral changes in G72/G30 transgenic mice

Abstract Genetic studies have implicated the evolutionary novel, primates-specific gene locus G72/G30 in schizophrenia, bipolar and panic disorders. It encodes for a protein LG72 whose function has been controversially discussed as putative regulator of the peroxisomal enzyme D-amino-acid-oxidase (D...

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Published in:European neuropsychopharmacology 2009-05, Vol.19 (5), p.339-348
Main Authors: Otte, David M, Bilkei-Gorzó, Andras, Filiou, Michaela D, Turck, Christoph W, Yilmaz, Öznur, Holst, Martin Ingo, Schilling, Karl, Abou-Jamra, Rami, Schumacher, Johannes, Benzel, Isabel, Kunz, Wolfram S, Beck, Heinz, Zimmer, Andreas
Format: Article
Language:English
Subjects:
Affective disorders
Animals
Behavior, Animal - physiology
Behavioral biology
Brain - cytology
Carrier Proteins - genetics
Compulsive Behavior - genetics
Dopamine Antagonists - pharmacology
G72
Haloperidol - pharmacology
Humans
Internal Medicine
Mice
Mice, Transgenic
Motor Activity - drug effects
Motor Activity - genetics
Motor Skills Disorders - genetics
Mouse models
Olfaction Disorders - genetics
Phencyclidine - pharmacology
Proteins - genetics
Psychiatry
RNA, Messenger - metabolism
Schizophrenia
Sensory Gating - drug effects
Sensory Gating - physiology
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Summary:Abstract Genetic studies have implicated the evolutionary novel, primates-specific gene locus G72/G30 in schizophrenia, bipolar and panic disorders. It encodes for a protein LG72 whose function has been controversially discussed as putative regulator of the peroxisomal enzyme D-amino-acid-oxidase (DAO), or as a mitochondrial protein, which promotes robust mitochondrial fragmentation in mammalian cell lines including human and rat primary neurons. Because of this conserved function we here have generated “humanized” BAC transgenic mice (G72Tg) expressing alternatively spliced G72 and G30 transcripts, and the LG72 protein. G72 expression is prominent in granular cells of the cerebellum, the hippocampus, the cortex and the olfactory bulb. Most strikingly, G72Tg mice displayed deficits in sensorimotor gating which could be reversed with haloperidol, increased sensitivity to PCP, motor-coordination deficits, increased compulsive behaviors and deficits in smell identification. These results demonstrate that expression of the human G72/G30 gene locus in mice produces behavioral phenotypes that are relevant to psychiatric disorders.
ISSN:0924-977X
1873-7862
DOI:10.1016/j.euroneuro.2008.12.009