Mannan, Ashraf U.

[["dc.bibliographiccitation.firstpage","788"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biology of Reproduction"],["dc.bibliographiccitation.lastpage","796"],["dc.bibliographiccitation.volume","69"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Nayernia, K."],["dc.contributor.author","Mueller, C."],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Adham, Ibrahim M."],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T10:36:20Z"],["dc.date.available","2018-11-07T10:36:20Z"],["dc.date.issued","2003"],["dc.description.abstract","The testicular haploid expressed gene (Theg) encodes for a novel similar to42.0-kDa nuclear protein, which is specifically expressed in spermatid cells. Its expression is upregulated by some unknown factor(s) from Sertoli cells. To elucidate the function of Theg protein and its role in spermatogenesis, we disrupted the Theg locus in mouse by homologous recombination. For functional dissection of the domain structure of the Theg protein, two different knockout approaches were undertaken. In the first knockout mouse (Th14), the C-terminal region of the Theg protein (amino acids 137-376) was deleted. Both Th14(+/-) and Th14(-/-) mice from genetic backgrounds of C57BL/6J X 129X1/ SvJ hybrid and 129X1/SvJ inbred exhibited a normal phenotype and were fertile. The testes of Th14(-/-) mice were smaller than those of Th14(+/-) and Th14(+/+) mice; however, the testicular morphology and the properties of sperm, including morphology and motility, from Th14(-/-) mice were similar to those of Th14(+/-) and Th14(+/+) mice. These results demonstrate that the C-terminal region of Theg (amino acids 137-376) does not play an important role in progression of spermatogenesis. In the second knockout mouse (Th15), we deleted the N-terminal domain of the Theg protein, which resulted in complete loss of Theg transcripts. Both Th15(+/-) and Th15(-/-) mice from genetic backgrounds C57BL/6J x 129X1/SvJ hybrid, C3H/J congenic, and 129X1/SvJ inbred appeared normal and were fertile, with no gross abnormalities detected in testicular morphology or sperm properties. Our results from both knockout mouse model systems clearly illustrate that Theg is not essential for spermatogenesis in the mouse."],["dc.identifier.doi","10.1095/biolreprod.103.017400"],["dc.identifier.isi","000184989100007"],["dc.identifier.pmid","12748127"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45299"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Study Reproduction"],["dc.relation.issn","0006-3363"],["dc.title","Male mice lacking the theg (Testicular haploid expressed gene) protein undergo normal spermatogenesis and are fertile"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","229"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neurogenetics"],["dc.bibliographiccitation.lastpage","238"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Roussa, Eleni"],["dc.contributor.author","Kraus, Cornelia"],["dc.contributor.author","Rickmann, Michael"],["dc.contributor.author","Maenner, Joerg"],["dc.contributor.author","Nayernia, K."],["dc.contributor.author","Krieglstein, Kerstin"],["dc.contributor.author","Reis, A."],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T10:43:34Z"],["dc.date.available","2018-11-07T10:43:34Z"],["dc.date.issued","2004"],["dc.description.abstract","We report a novel spontaneous mutation named nax in mice, which exhibit delayed hair appearance and ataxia in a homozygote state. Histological analyses of nax brain revealed an overall impairment of the cerebellar cortex. The classical cortical cytoarchitecture was disrupted, the inner granule cell layer was not obvious, the Purkinje cells were not aligned as a Purkinje cell layer, and Bergmann glias did not span the molecular layer. Furthermore, histological analyses of skin showed that the hair follicles were also abnormal. We mapped the nax locus between marker D2Mit158 and D2Mit100 within a region of 800 kb in the middle of chromosome 2 and identified a missense mutation (Gly244Glu) in Acp2, a lysosomal monoesterase. The Glu244 mutation does not affect the stability of the Acp2 transcript, however it renders the enzyme inactive. Ultrastructural analysis of nax cerebellum showed lysosomal storage bodies in nucleated cells, suggesting progressive degeneration as the underlying mechanism. Identification of Acp2 as the gene mutated in nax mice provides a valuable model system for studying the role of Acp2 in cerebellum and skin homeostasis."],["dc.identifier.doi","10.1007/s10048-004-0197-9"],["dc.identifier.isi","000226285100005"],["dc.identifier.pmid","15503243"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47086"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1364-6745"],["dc.title","Mutation in the gene encoding lysosomal acid phosphatase (Acp2) causes cerebellum and skin malformation in mouse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","99"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Neurology"],["dc.bibliographiccitation.lastpage","105"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Klimpe, Sven"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Wellek, B."],["dc.contributor.author","Shoukier, Moneef"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T09:01:10Z"],["dc.date.available","2018-11-07T09:01:10Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP. Methods: A reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed. Results: We have characterized the consequence of two novel splice-site mutations (c.1493 + 1G > A and c.1414-1G > A) in the SPAST gene in two different families with pure HSP. The RT-PCR analysis revealed that both spastin mutations are indeed splice-site mutations and cause skipping of exon 12. Furthermore, RT-PCR data suggested that these splice-site mutations may cause leaky splicing. By means of a quantitative allele-specific expression assay, we could confirm that both splice-site mutations cause leaky splicing, as the relative expression of the exon 12-skipped transcript was reduced (21.1 +/- 3.6 compared to expected 50%). Conclusions: Our finding supports a \"threshold-effect-model\" for functional spastin in HSP. A higher level (78.8 +/- 3.9%) of functional spastin than the expected ratio of 50% owing to leaky splicing might cause late age at onset of HSP. Remarkably, we could show that a quantitative allele-specific expression assay is a simple and effective tool to evaluate the role of most types of spastin splice-site mutations in HSP."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Institute internal fund"],["dc.identifier.doi","10.1111/j.1468-1331.2010.03079.x"],["dc.identifier.isi","000285356300015"],["dc.identifier.pmid","20491894"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24351"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1351-5101"],["dc.title","Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","93"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurogenetics"],["dc.bibliographiccitation.lastpage","103"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Boehm, J."],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Rauber, A."],["dc.contributor.author","Byrne, P. C."],["dc.contributor.author","Neesen, J."],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T09:55:10Z"],["dc.date.available","2018-11-07T09:55:10Z"],["dc.date.issued","2006"],["dc.description.abstract","Spastin, an ATPase belonging to the AAA family of proteins is most commonly mutated in autosomal dominant hereditary spastic paraplegias (HSP). Spastin is a multifaceted protein with versatile role in cellular events, principally involved in microtubule dynamics. To gain further insight into the molecular function of spastin, we used the yeast two-hybrid approach to identify novel interacting partners of spastin. Using spastin as bait, we identified reticulon 1 (RTN1) and reticulon 3 (RTN3) as potential spastin interacting proteins. RTN1 and RTN3 belong to the reticulon (RTN) gene family, which are primarily expressed in the endoplasmic reticulum. Moreover, RTN1 is known to play a role in vesicular transport processes. Using in vitro and in vivo immunoprecipitation experiments, we were able to demonstrate that RTN1 interacts specifically with spastin. Intracellular distribution studies using immunostaining and overexpression of epitope-tagged protein revealed an obvious colocalization of spastin and RTN1 in discrete vesicles in the cytoplasm. Spastin mediates its interaction with RTN1 through its N-terminal region containing a microtubule-interacting and trafficking domain. It is interesting to note that the aberrant intracellular distribution of a truncated spastin protein was rescued by coexpression with RTN1, which highlights the physiological significance of this interaction. Our findings strengthen the hypothesis that disruption of intracellular vesicular transport processes could cause HSP. It is interesting to note that RTN1 is localized to 14q23.1 where SPG15 locus was mapped. Therefore, we considered RTN1 as a candidate gene for the SPG15 locus, but our mutational analysis possibly excludes RTN1 as causative gene."],["dc.identifier.doi","10.1007/s10048-006-0034-4"],["dc.identifier.isi","000237325600003"],["dc.identifier.pmid","16602018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36690"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1364-6745"],["dc.title","Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with reticulon 1 an endoplasmic reticulum protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","351"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","357"],["dc.bibliographiccitation.volume","79"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Krawen, Philip"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Boehm, Johann"],["dc.contributor.author","Chronowska, Agnieszka"],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Neesen, Juergen"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T09:26:29Z"],["dc.date.available","2018-11-07T09:26:29Z"],["dc.date.issued","2006"],["dc.description.abstract","Spastin, the most commonly mutated protein in the autosomal dominant form of hereditary spastic paraplegia (ADHSP) has been suggested to be involved in vesicular cargo trafficking; however, a comprehensive function of spastin has not yet been elucidated. To characterize the molecular function of spastin, we used the yeast two-hybrid approach to identify new interacting partners of spastin. Here, we report ZFYVE27, a novel member of the FYVE-finger family of proteins, as a specific spastin-binding protein, and we validate the interaction by both in vivo coimmunoprecipitation and colocalization experiments in mammalian cells. More importantly, we report a German family with AD-HSP in which ZFYVE27 (SPG33) is mutated; furthermore, we demonstrate that the mutated ZFYVE27 protein shows an aberrant intracellular pattern in its tubular structure and that its interaction with spastin is severely affected. We postulate that this specific mutation in ZFYVE27 affects neuronal intracellular trafficking in the corticospinal tract, which is consistent with the pathology of HSP."],["dc.identifier.doi","10.1086/504927"],["dc.identifier.isi","239040400016"],["dc.identifier.pmid","16826525"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30313"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Univ Chicago Press"],["dc.relation.issn","0002-9297"],["dc.title","ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","268"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Arygriou, L."],["dc.contributor.author","Pauli, Silke"],["dc.contributor.author","Sauter, Simone M."],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:17:25Z"],["dc.date.available","2018-11-07T11:17:25Z"],["dc.date.issued","2008"],["dc.description.abstract","The SPG4 gene is frequently mutated in autosomal dominant form of hereditary spastic paraplegia (HSP). We report that the compound heterozygous sequence variants S44L, a known polymorphism, and c.1687G > A, a novel mutation in SPG4 cause a severe form of HSP in a patient. The family members carrying solely c.1687G > A mutation are asymptomatic for HSP. The reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the c.1687G > A mutation is a splice site mutation and causes skipping of the exon 15 of spastin. Furthermore, quantification of RT-PCR products by sequencing and quantification of allele-specific expression by pyrosequencing assay revealed that c.1687G > A is a leaky or hypomorphic splice site mutation. At the protein level, c.1687G > A mutation in SPG4 leads to E563K substitution. In ex vivo study, about 10% of cells expressing E563K mutant spastin showed filamentous expression pattern, suggesting a hypomorphic effect at the protein level. Collectively, our results suggest that S44L in association with c.1687G > A (E563K) drops the functional level of spastin below a threshold limit sufficient to manifest HSP."],["dc.identifier.doi","10.1111/j.1399-0004.2007.00953.x"],["dc.identifier.isi","000252929000012"],["dc.identifier.pmid","18190593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54802"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0009-9163"],["dc.title","Compound heterozygosity in the SPG4 gene causes hereditary spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","431"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular Reproduction and Development"],["dc.bibliographiccitation.lastpage","438"],["dc.bibliographiccitation.volume","66"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Nica, G."],["dc.contributor.author","Nayernia, K."],["dc.contributor.author","Mueller, C."],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T10:34:29Z"],["dc.date.available","2018-11-07T10:34:29Z"],["dc.date.issued","2003"],["dc.description.abstract","The murine calgizzarin like gene (Cal) encodes for a calcium binding protein, which belongs to the S100 family of EF-hand proteins. It is specifically expressed in Sertoli cells in the testis and its expression is down-regulated by unknown factor(s) from spermatocytes/spermatids. In this paper, we show by transfection of a fusion protein of green fluorescent protein and Cal protein into NIH3T3 cells, that the expression of Cal is restricted only in the cytoplasm of the cell. A differentially regulated cytoplasmic expression of the Cal in Sertoli cells during mouse development suggests that Cal might play an important role during spermatogenesis. In order to elucidate the function of the Cal protein in the spermatogenesis, we disrupted the Cal locus in mouse by homologous recombination. In our knockout mouse, we deleted exon 2 and exon 3 of the Cal gene and replaced them with a neomycin cassette, which resulted in a complete loss of the Cal transcript. Male and female Cal4(+/-) and Cal4(-/-) mice from genetic backgrounds C57BL/6J x 129X1/SvJ hybrid and 129X1/SvJ inbred exhibited normal phenotype and were fertile. An intensive phenotypic analysis showed no gross abnormalities in testis morphology. The lack of the Cal protein also does not affect the parameters of sperm, as they are able to fertilize the oocytes in a competent manner, which is comparable to wild-type sperm. Collectively our results demonstrate that Cal is a nonessential protein and it does not play an important role in mouse spermatogenesis or in process of fertilization. (C) 2003 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/mrd.10367"],["dc.identifier.isi","000186391400012"],["dc.identifier.pmid","14579419"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44884"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1040-452X"],["dc.title","Calgizarrin like gene (Cal) deficient mice undergo normal spermatogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","613"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","624"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Swapna, Lakshmipuram S."],["dc.contributor.author","Srinivasan, Narayanaswamy"],["dc.contributor.author","Mannan, Ashraf U."],["dc.date.accessioned","2018-11-07T11:13:37Z"],["dc.date.available","2018-11-07T11:13:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Spastin, a member of the ATPases associated with various cellular activities (AAA) family of proteins, is the most frequently mutated in hereditary spastic paraplegia. The defining feature of the AAA proteins is a structurally conserved AAA domain which assembles into an oligomer. By chemical cross-linking and gel filtration chromatography, we show that spastin oligomerizes into a hexamer. Furthermore, to gain a comprehensive overview of the oligomeric structure of spastin, we generated a structural model of the AAA domain of spastin using template structure of VPS4B and p97/VCP. The generated model of spastin provided us with a framework to classify the identified missense mutations in the AAA domain from hereditary spastic paraplegia patients into different structural/functional groups. Finally, through co-localization studies in mammalian cells, we show that E442Q mutant spastin acts in a dominant negative fashion and causes redistribution of both wild-type spastin monomer and spastin interacting protein, RTN1 into filamentous microtubule bundles."],["dc.identifier.doi","10.1111/j.1471-4159.2008.05414.x"],["dc.identifier.isi","000257708000011"],["dc.identifier.pmid","18410514"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53940"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3042"],["dc.title","Spastin oligomerizes into a hexamer and the mutant spastin (E442Q) redistribute the wild-type spastin into filamentous microtubule"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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.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"]]