Arunachalam, Jayamuruga Pandian

[["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","290"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cytogenetic and Genome Research"],["dc.bibliographiccitation.lastpage","297"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Kifayathullah, L. A."],["dc.contributor.author","Arunachalam, J. P."],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Agbemenyah, H. Y."],["dc.contributor.author","Laccone, Franco A."],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:47:29Z"],["dc.date.available","2018-11-07T08:47:29Z"],["dc.date.issued","2010"],["dc.description.abstract","The MECP2 gene, located at Xq28, encodes methyl-CpG-binding protein 2 (MeCP2), which is frequently mutated (up to 90%) in Rett syndrome (RTT). RTT is a progressive neuro-developmental disorder, which affects primarily girls during early childhood and it is one of the most common causes of mental retardation in females. R270X is one of the most frequent recurrent MECP2 mutations among RTT cohorts. The R270X mutation resides within the TRD-NLS (Transcription Repression Domain-Nuclear Localization Signal) region of MeCP2 and causes a more severe clinical phenotype with increased mortality as compared to other mutations. To evaluate the functional role of the R270X mutation, we generated a transgenic mouse model expressing MeCP2(270_EGFP) (human mutation equivalent) by BAC recombineering. The expression pattern of MeCP2(270_EGFP) was similar to that of endogenous MeCP2. Strikingly, MeCP2(270_EGFP) localizes in the nucleus, contrary to the conjecture that R270X could cause disruption of the NLS. In primary hippocampal cells, we show that MeCP2(270_EGFP) was expressed in astrocytes by colocalization with the astrocyte-specific marker glial fibrillary acidic protein. Our data showing expression of MeCP2(270_EGFP) in transgenic mice astrocytes further reinforce the recent findings concerning the expression of MeCP2 in the glial cells. Copyright (C) 2010 S. Karger AG, Basel"],["dc.description.sponsorship","DFG-Research Center for Molecular Physiology"],["dc.identifier.doi","10.1159/000315906"],["dc.identifier.isi","000280683800005"],["dc.identifier.pmid","20625242"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20963"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.relation.issn","1424-8581"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","MeCP2(270) Mutant Protein Is Expressed in Astrocytes as well as in Neurons and Localizes in the Nucleus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]