Behavioral changes in G72/G30 transgenic mice.
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.
Otte
David M
DM
Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
Bilkei-Gorzó
Andras
A
Filiou
Michaela D
MD
Turck
Christoph W
CW
Yilmaz
Oznur
O
Holst
Martin Ingo
MI
Schilling
Karl
K
Abou-Jamra
Rami
R
Schumacher
Johannes
J
Benzel
Isabel
I
Kunz
Wolfram S
WS
Beck
Heinz
H
Zimmer
Andreas
A
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
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