title: 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 (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.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Otte
authors.forename: Andras
authors.initials: A
authors.lastname: Bilkei-Gorzó
authors.forename: Michaela D
authors.initials: MD
authors.lastname: Filiou
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.forename: Oznur
authors.initials: O
authors.lastname: Yilmaz
authors.forename: Martin Ingo
authors.initials: MI
authors.lastname: Holst
authors.forename: Karl
authors.initials: K
authors.lastname: Schilling
authors.forename: Rami
authors.initials: R
authors.lastname: Abou-Jamra
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Isabel
authors.initials: I
authors.lastname: Benzel
authors.forename: Wolfram S
authors.initials: WS
authors.lastname: Kunz
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics*; D003192:Compulsive Behavior / Q000235:genetics; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D019957:Motor Skills Disorders / Q000235:genetics; D000857:Olfaction Disorders / Q000235:genetics; D010622:Phencyclidine / Q000494:pharmacology; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; C488199:DAOAAS gene product, human; D018492:Dopamine Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D010622:Phencyclidine; D006220:Haloperidol