Mannan, Ashraf U.

[["dc.bibliographiccitation.artnumber","e94327"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Bailey, Karen"],["dc.contributor.author","Balaei, Maryam Rahimi"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Del Bigio, Marc R."],["dc.contributor.author","Marzban, Hassan"],["dc.date.accessioned","2018-11-07T09:41:17Z"],["dc.date.available","2018-11-07T09:41:17Z"],["dc.date.issued","2014"],["dc.description.abstract","The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous mutation in Acp2 results in severe cerebellar defects. These include a reduced size, abnormal lobulation, and an apparent anterior cerebellar disorder with an absent or hypoplastic vermis. Based on differential gene expression in the cerebellum, the mouse cerebellar cortex can normally be compartmentalized anteroposteriorly into four transverse zones and mediolaterally into parasagittal stripes. In this study, immunohistochemistry was performed using various Purkinje cell compartmentation markers to examine their expression patterns in the Acp2 mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin II and PLC beta 4 showed similar expression patterns in the nax mutant and wild type cerebellum. However, fewer stripes were found in the anterior zone of the nax mutant, which could be due to a lack of Purkinje cells or altered expression of the stripe markers. HSP25 expression was uniform in the central zone of the nax mutant cerebellum at around postnatal day (P) 18-19, suggesting that HSP25 immunonegative Purkinje cells are absent or delayed in stripe pattern expression compared to the wild type. HSP25 expression became heterogeneous around P22-23, with twice the number of parasagittal stripes in the nax mutant compared to the wild type. Aside from reduced size and cortical disorganization, both the posterior zone and nodular zone in the nax mutant appeared less abnormal than the rest of the cerebellum. From these results, it is evident that the anterior zone of the nax mutant cerebellum is the most severely affected, and this extends beyond the primary fissure into the rostral central zone/vermis. This suggests that ACP2 has critical roles in the development of the anterior cerebellum and it may regulate anterior and central zone compartmentation."],["dc.description.sponsorship","Manitoba Health Research Council (MHRC); University of Manitoba"],["dc.identifier.doi","10.1371/journal.pone.0094327"],["dc.identifier.isi","000336909100054"],["dc.identifier.pmid","24722417"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10494"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33696"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Purkinje Cell Compartmentation in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant Mouse (Nax - Naked-Ataxia Mutant Mouse)"],["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"]]

[["dc.bibliographiccitation.firstpage","617"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","621"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Bonn, Florian"],["dc.contributor.author","Pantakani, Krishna"],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Langer, Thomas"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:43:34Z"],["dc.date.available","2018-11-07T08:43:34Z"],["dc.date.issued","2010"],["dc.description.abstract","An autosomal recessive form of hereditary spastic paraplegia (AR-HSP) is primarily caused by mutations in the SPG7 gene, which codes for paraplegin, a subunit of the hetero-oligomeric m-AAA protease in mitochondria. In the current study, sequencing of the SPG7 gene in the genomic DNA of 25 unrelated HSP individuals/families led to the identification of two HSP patients with compound heterozygous mutations (p.G349S/p.W583C and p.A510V/p.N739KfsX741) in the coding sequence of the SPG7 gene. We used a yeast complementation assay to evaluate the functional consequence of novel SPG7 sequence variants detected in the HSP patients. We assessed the proteolytic activity of hetero-oligomeric m-AAA proteases composed of paraplegin variant(s) and proteolytically inactive forms of AFG3L2 (AFG3L2(E575Q) or AFG3L2(K354A)) upon expression in m-AAA protease-deficient yeast cells. We demonstrate that the newly identified paraplegin variants perturb the proteolytic function of hetero-oligomeric m-AAA protease. Moreover, commonly occurring silent polymorphisms such as p.T503A and p.R688Q could be distinguished from mutations (p.G349S, p.W583C, p.A510V, and p.N739KfsX744) in our HSP cohort. The yeast complementation assay thus can serve as a reliable system to distinguish a pathogenic mutation from a silent polymorphism for any novel SPG7 sequence variant, which will facilitate the interpretation of genetic data for SPG7. Hum Mutat 31:617-621, 2010. (C) 2010 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/humu.21226"],["dc.identifier.isi","000277779100013"],["dc.identifier.pmid","20186691"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6230"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20000"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1059-7794"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Functional Evaluation of Paraplegin Mutations by a Yeast Complementation Assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e29584"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Pantakani, D. V. Krishna"],["dc.contributor.author","Czyzewska, Marta M."],["dc.contributor.author","Sikorska, Anna"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T08:48:45Z"],["dc.date.available","2018-11-07T08:48:45Z"],["dc.date.issued","2011"],["dc.description.abstract","ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(Delta HR3) failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(Delta HR3) was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT)), it exerted a dominant negative effect on ZFYVE27(WT) as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [MA 3344-2]"],["dc.identifier.doi","10.1371/journal.pone.0029584"],["dc.identifier.isi","000300676300068"],["dc.identifier.pmid","22216323"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8210"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21300"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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"]]

[["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"]]