Tantra, Martesa

[["dc.bibliographiccitation.artnumber","181"],["dc.bibliographiccitation.journal","Frontiers in Behavioral Neuroscience"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Dere, Ekrem"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Lu, Derek"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Chowdhury, Kamal"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2014"],["dc.description.abstract","Autism-spectrum disorders (ASD) are heterogeneous, highly heritable neurodevelopmental conditions affecting around 0.5% of the population across cultures, with a male/female ratio of approximately 4:1. Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g., through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar phenotypical consequences. Ambra1, strongly expressed in cortex, hippocampus, and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1 (+/-) females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups, which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1 (+/-) mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1 (+/-) females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation."],["dc.format.extent","19"],["dc.identifier.doi","10.3389/fnbeh.2014.00181"],["dc.identifier.gro","3150538"],["dc.identifier.pmid","24904333"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11695"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7311"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject","Ambra1; autism composite score; autophagy; cognitive rigidity; heterozygous null mutant mice; repetitive behavior; social interaction; ultrasound communication"],["dc.title","Heterozygous Ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1143"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.bibliographiccitation.lastpage","1149"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Mohd Jofrry, Sue"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Jensen, Niels"],["dc.contributor.author","Ostmeier, Katrin"],["dc.contributor.author","Lühder, F."],["dc.contributor.author","Probst, Christian"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Gillis, M."],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Assogna, F."],["dc.contributor.author","Spalletta, Gianfranco"],["dc.contributor.author","Stöcker, W."],["dc.contributor.author","Schulz, Thomas F."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2014"],["dc.description.abstract","In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function."],["dc.identifier.doi","10.1038/mp.2013.110"],["dc.identifier.gro","3150565"],["dc.identifier.pmid","23999527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7339"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.journal","Molecular Medicine"],["dc.bibliographiccitation.lastpage","148"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Man, Kwun-nok M"],["dc.contributor.author","Müller-Ribbe, Katja"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Shin, Yong"],["dc.contributor.author","Augustin, Iris"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders."],["dc.identifier.doi","10.2119/molmed.2013.00033"],["dc.identifier.gro","3150563"],["dc.identifier.pmid","23698091"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7337"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","195"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","American Journal of Pathology"],["dc.bibliographiccitation.lastpage","210"],["dc.bibliographiccitation.volume","183"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Mollajew, Rustam"],["dc.contributor.author","Arunachalam, Jayamuruga P."],["dc.contributor.author","Can, Karolina"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Laccone, Franco A."],["dc.date.accessioned","2017-09-07T11:45:46Z"],["dc.date.available","2017-09-07T11:45:46Z"],["dc.date.issued","2013"],["dc.description.abstract","An intriguing finding about the gene encoding methyl-CpG binding protein 2 (MeCP2) is that the loss-of-function mutations cause Rett syndrome and duplication (gain-of-function) of MECP2 leads to another neurological disorder termed MECP2 duplication syndrome. To ensure proper neurodevelopment, a precise regulation of MeCP2 expression is critical, and any gain or loss of MeCP2 over a narrow threshold level may lead to postnatal neurological impairment. To evaluate MeCP2 dosage effects, we generated Mecp2(WT_EGFP) transgenic (TG) mouse in which MeCP2 (endogenous plus TG) is mildly overexpressed (approximately 1.5×). The TG MeCP2(WT_EGFP) fusion protein is functionally active, as cross breeding of these mice with Mecp2 knockout mice led to alleviation of major phenotypes in the null mutant mice, including premature lethality. To characterize the Mecp2(WT_EGFP) mouse model, we performed an extensive battery of behavioral tests, which revealed that these mice manifest increased aggressiveness and higher pentylenetetrazole (PTZ)-induced seizure propensity. Evaluation of neuronal parameters revealed a reduction in the number of tertiary branching sites and increased spine density in Mecp2(WT_EGFP) transgenic (TG) neurons. Treatment of TG neurons with epileptogenic compound-PTZ led to a marked increase in amplitude and frequency of calcium spikes. Based on our ex vivo and in vivo data, we conclude that epileptic seizures are manifested as the first symptom when MeCP2 is mildly overexpressed in mice."],["dc.identifier.doi","10.1016/j.ajpath.2013.03.019"],["dc.identifier.gro","3150451"],["dc.identifier.pmid","23684790"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7216"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","166"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","175"],["dc.bibliographiccitation.volume","275"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Kröcher, Tim"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Winkler, Daniela"],["dc.contributor.author","Röckle, Iris"],["dc.contributor.author","Jatho, Jasmin"],["dc.contributor.author","Burkhardt, Hannelore"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Gerardy-Schahn, Rita"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Hildebrandt, Herbert"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2014"],["dc.description.abstract","The neural cell adhesion molecule (NCAM) and its functionally linked polysialyltransferases, ST8SIA2 and ST8SIA4, are crucial for synaptic plasticity. Variations in encoding genes have been associated with mental illness. Since cannabinoids can alter NCAM polysialylation, we hypothesized that delta-9-tetrahydrocannabinol (Δ9-THC) might act as environmental 'second hit' regarding cognition of St8sia2(-/-) mice. These mice show per se minor behavioral abnormalities, consisting of reduced anxiety and mild cognitive deficits. Chronic Δ9-THC treatment of juvenile male wildtype mice (St8sia2(+/+)) (7mg/kg every other day over 3 weeks) did not appreciably affect cognition. St8sia2(-/-) mice, however, displayed a synergistic negative consequence of Δ9-THC on learning/memory, accompanied by polysialic acid-free NCAM-180 reduction in hippocampus and polysialic acid increase in dentate outer molecular layer. These synergistic effects became obvious only months after the last Δ9-THC. We conclude that juvenile cannabis exposure may cause delayed but lasting damage on cognition in subjects genetically predisposed to altered NCAM polysialylation."],["dc.identifier.doi","10.1016/j.bbr.2014.08.062"],["dc.identifier.gro","3150537"],["dc.identifier.pmid","25200516"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7310"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.subject","Learning index; NCAM; PolySia; Reference memory; Working memory; Δ-9-THC"],["dc.title","St8sia2 deficiency plus juvenile cannabis exposure in mice synergistically affect higher cognition in adulthood"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","159"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","164"],["dc.bibliographiccitation.volume","270"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Krueger, Dilja"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:27Z"],["dc.date.available","2017-09-07T11:46:27Z"],["dc.date.issued","2014"],["dc.description.abstract","Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Lossof-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism.Adult Nlgn4 null mutant (Nlgn4−/−) mice are a construct valid model of human autism, with both gendersdisplaying a remarkable autistic phenotype, including deficits in social interaction and communication aswell as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonataland juvenile Nlgn4−/− mice have not been reported yet. The present study has been designed tosystematically investigate in male and female Nlgn4−/− pups versus wildtype littermates (WT, Nlgn4+/+)developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development,followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexesand neuromotor coordination, did not yield any differences between Nlgn4−/− and their WT littermates.USV in pups (PND8–9) in response to brief separation from their mothers revealed remarkable gendereffects, and a genotype influence in females regarding latency to first call. In juveniles (PND22–23),USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotypeeffect with reduced USV in Nlgn4−/− mice, and again a more prominent phenotype in females. Together,these data support an early manifestation of communication deficits in Nlgn4−/− mice that appear morepronounced in immature females with their overall stronger USV as compared to males."],["dc.identifier.doi","10.1016/j.bbr.2014.05.019"],["dc.identifier.gro","3150517"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7290"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.subject","Neuroligin-4; C57BL/6J; Ultrasound or ultrasonic vocalization; Neonatal milestones; Neonatal development; Gender"],["dc.title","Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1130"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","1145"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Agarwal, Amit"],["dc.contributor.author","Zhang, Mingyue"],["dc.contributor.author","Trembak-Duff, Irina"],["dc.contributor.author","Unterbarnscheidt, Tilmann"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Souza, Daniel Martins de"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Brzózka, Magdalena"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Berning, Sebastian"],["dc.contributor.author","Teng, Zenghui"],["dc.contributor.author","Gummert, Maike N."],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Guest, Peter C."],["dc.contributor.author","Willig, Katrin I."],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Bahn, Sabine"],["dc.contributor.author","Rossner, Moritz J."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Zhang, Weiqi"],["dc.contributor.author","Schwab, Markus H."],["dc.date.accessioned","2017-09-07T11:45:36Z"],["dc.date.available","2017-09-07T11:45:36Z"],["dc.date.issued","2014"],["dc.description.abstract","Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an \"optimal' level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect."],["dc.identifier.doi","10.1016/j.celrep.2014.07.026"],["dc.identifier.gro","3142068"],["dc.identifier.isi","000341573500021"],["dc.identifier.pmid","25131210"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4189"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.title","Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","662"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","684"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Giegling, Ina"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Castillo Venzor, Aracely"],["dc.contributor.author","Konte, Bettina"],["dc.contributor.author","Erbaba, Begun"],["dc.contributor.author","Hartmann, Annette M."],["dc.contributor.author","Tarami, Asieh"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:35Z"],["dc.date.available","2017-09-07T11:46:35Z"],["dc.date.issued","2014"],["dc.description.abstract","The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior."],["dc.identifier.doi","10.1002/emmm.201303744"],["dc.identifier.gro","3150551"],["dc.identifier.pmid","24648499"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7325"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mild expression differences of MECP2 influencing aggressive social behavior"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]