Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G72 is a strong candidate susceptibility gene for schizophrenia and bipolar disorder, whose function remains enigmatic. Here we show that one splicing isoform of the gene (LG72) encodes for a mitochondrial protein. We also provide convergent lines of evidence that increase of endogenous or exogenous G72 levels promotes robust mitochondrial fragmentation in mammalian cell lines and primary neurons, which proceeds in a manner that does not depend on induction of apoptosis or alteration in mitochondrial transmembrane potential. Finally, we show that increase in G72 levels in immature primary neurons is accompanied by a marked increase in dendritic arborization. By contrast, we failed to confirm the originally proposed functional interaction between G72 and D-amino acid oxidase (DAO) in two tested cell lines. Our results suggest an alternative role for G72 in modulating mitochondrial function.
 ...
PMID:Evidence implicating the candidate schizophrenia/bipolar disorder susceptibility gene G72 in mitochondrial function. 1768 99

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.
 ...
PMID:Behavioral changes in G72/G30 transgenic mice. 1918 79

G72/G30 is a primate-specific locus that has been repeatedly implicated as a risk factor in genetic studies of schizophrenia. The function of the longest G72 splice variant (LG72 protein) encoded by this locus is not fully understood. To investigate the role of the LG72 protein in vivo, we have generated transgenic (G72Tg) mice carrying the G72/G30 locus that exhibit schizophrenia-like symptoms. We investigated protein expression alterations in the cerebella of G72Tg compared to wild type (WT) mice using a proteomics approach based on in vivo(15)N metabolic labeling and quantitative mass spectrometry (MS). Our data revealed expression level differences of proteins involved in myelin-related processes, oxidative stress and mitochondrial function. Furthermore, in silico pathway analyses suggested common regulators and targets for the observed protein alterations. Our work sheds light on the functional role of the LG72 protein and pinpoints molecular correlates of schizophrenia-like behavior.
 ...
PMID:Myelination and oxidative stress alterations in the cerebellum of the G72/G30 transgenic schizophrenia mouse model. 2288 23

Schizophrenia is a human mental disorder that affects an individual's thoughts, perception, affect and behavior, which is caused by a complex interaction of genetic and environmental factors. Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in the etiology of schizophrenia and other psychiatric disorders. This gene encodes the protein LG72, which has been discussed as a modulator of the peroxisomal enzyme d-amino-acid-oxidase (DAO), or, alternatively as a mitochondrial protein. Recently, G72 transgenic (G72Tg) mice were generated that express the protein throughout the brain. These mice show several behavioral deficits that are related to schizophrenia. Further, G72Tg mice have a reduced activity of mitochondrial complex I, with a concomitantly increased production of reactive oxygen species, as well as deficits in short-term plasticity. Results from these studies demonstrate that expression of the human G72/G30 gene locus in mice produces behavioral phenotypes that are relevant to schizophrenia. They implicate LG72-induced mitochondrial and synaptic defects as a possible pathomechanism of this disease.
 ...
PMID:Involvement of the primate specific gene G72 in schizophrenia: From genetic studies to pathomechanisms. 2309 56

The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially expressed in transgenic mice compared with wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.
...
PMID:Expression of the G72/G30 gene in transgenic mice induces behavioral changes. 2333 43

Genetic studies have linked the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in the etiology of schizophrenia and other psychiatric disorders. However, the function of the protein encoded by this locus, LG72, is currently controversially discussed. Some studies have suggested that LG72 binds to and regulates the activity of the peroxisomal enzyme D-amino-acid-oxidase, while others proposed an alternative role of this protein due to its mitochondrial location in vitro. Studies with transgenic mice expressing LG72 further suggested that high levels of LG72 lead to an impairment of mitochondrial functions with a concomitant increase in reactive oxygen species production. In the present study, we now performed extensive interaction analyses and identified the mitochondrial methionine-R-sulfoxide reductase B2 (MSRB2) as a specific interaction partner of LG72. MSRB2 belongs to the MSR protein family and functions in mitochondrial oxidative stress defense. Based on our results, we propose that LG72 is involved in the regulation of mitochondrial oxidative stress.
...
PMID:Identification of the mitochondrial MSRB2 as a binding partner of LG72. 2507 55