Kästner, Anne

[["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","41"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","49"],["dc.bibliographiccitation.volume","251"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Winkler, Daniela"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Krueger, Dilja"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Ritter, Caroline"],["dc.contributor.author","Jatho, Jasmin"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","Bourgeron, Thomas"],["dc.contributor.author","Fischer, Julia"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:47:38Z"],["dc.date.available","2017-09-07T11:47:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a 'synapse disorder'. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity."],["dc.identifier.doi","10.1016/j.bbr.2012.11.016"],["dc.identifier.gro","3142307"],["dc.identifier.isi","000322927700006"],["dc.identifier.pmid","23183221"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6831"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0166-4328"],["dc.subject","Social interaction; Nest building; Grooming; Repetitive behaviors; Stereotypies; Ultra-sound vocalization; Gender differences; ASD"],["dc.title","Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e254"],["dc.bibliographiccitation.journal","Translational Psychiatry"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Klugmann, M."],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Patzig, Julia"],["dc.contributor.author","Monasterio-Schrader, P. D."],["dc.contributor.author","Strenzke, N."],["dc.contributor.author","Flügge, G."],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Pawlak, R."],["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","2013"],["dc.description.abstract","Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia."],["dc.format.extent","12"],["dc.identifier.doi","10.1038/tp.2013.28"],["dc.identifier.gro","3150562"],["dc.identifier.pmid","23632458"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10616"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7336"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject","chromosome 4; GPM6A; human pedigree; miR124; mouse mutant; panic disorder"],["dc.title","A single gene defect causing claustrophobia"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["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"]]