@article{TeutschbeinHaydnSamansetal.2010,
  author    = {Teutschbein, Janka and Haydn, Johannes M. and Samans, Birgit and Krause, Michael and Eilers, Martin and Schartl, Manfred and Meierjohann, Svenja},
  title     = {Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67900},
  year      = {2010},
  abstract  = {Background: Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods: Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results: Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion: Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.},
  language  = {en}
}
@article{TomaszkiewiczChalopinSchartletal.2014,
  author    = {Tomaszkiewicz, Marta and Chalopin, Domitille and Schartl, Manfred and Galiana, Delphine and Volff, Jean-Nicolas},
  title     = {A multicopy Y-chromosomal SGNH hydrolase gene expressed in the testis of the platyfish has been captured and mobilized by a Helitron transposon},
  series = {BMC Genetics},
  volume    = {15},
  journal   = {BMC Genetics},
  number    = {44},
  doi       = {10.1186/1471-2156-15-44},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116746},
  year      = {2014},
  abstract  = {Background: Teleost fish present a high diversity of sex determination systems, with possible frequent evolutionary turnover of sex chromosomes and sex-determining genes. In order to identify genes involved in male sex determination and differentiation in the platyfish Xiphophorus maculatus, bacterial artificial chromosome contigs from the sex-determining region differentiating the Y from the X chromosome have been assembled and analyzed. Results: A novel three-copy gene called teximY (for testis-expressed in Xiphophorus maculatus on the Y) was identified on the Y but not on the X chromosome. A highly related sequence called texim1, probably at the origin of the Y-linked genes, as well as three more divergent texim genes were detected in (pseudo) autosomal regions of the platyfish genome. Texim genes, for which no functional data are available so far in any organism, encode predicted esterases/lipases with a SGNH hydrolase domain. Texim proteins are related to proteins from very different origins, including proteins encoded by animal CR1 retrotransposons, animal platelet-activating factor acetylhydrolases (PAFah) and bacterial hydrolases. Texim gene distribution is patchy in animals. Texim sequences were detected in several fish species including killifish, medaka, pufferfish, sea bass, cod and gar, but not in zebrafish. Texim-like genes are also present in Oikopleura (urochordate), Amphioxus (cephalochordate) and sea urchin (echinoderm) but absent from mammals and other tetrapods. Interestingly, texim genes are associated with a Helitron transposon in different fish species but not in urochordates, cephalochordates and echinoderms, suggesting capture and mobilization of an ancestral texim gene in the bony fish lineage. RT-qPCR analyses showed that Y-linked teximY genes are preferentially expressed in testis, with expression at late stages of spermatogenesis (late spermatids and spermatozeugmata). Conclusions: These observations suggest either that TeximY proteins play a role in Helitron transposition in the male germ line in fish, or that texim genes are spermatogenesis genes mobilized and spread by transposable elements in fish genomes.},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery : A Web Tool for Easy Associative Querying of Transcriptome Data},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76088},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deepsequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  subject      = {CrossQuery},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery: A Web Tool for Easy Associative Querying of Transcriptome Data},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0028990},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134787},
  pages     = {e28990},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deep-sequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  language  = {en}
}
@article{WinklerHongWittbrodtetal.1992,
  author    = {Winkler, Christoph and Hong, Yunhan and Wittbrodt, Joachim and Schartl, Manfred},
  title     = {Analysis of heterologous and homologous promoters and enhancers in vitro and in vivo by gene transfer into Japanese medaka (Oryzias latipes) and Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86796},
  year      = {1992},
  abstract  = {Efficient expression systems are required for analysis of gene regulation and function in teleost fish. To develop such systems, a nurober of inducible or constitutive promoter and enhancer sequences of fish or higher vertebrate origin were tested for activity in a variety of fish celllines andin embryos of the Japanese medaka fish (Oryzias latipes) and Xiphophorus. The activity of the different promoterenhancer combinations were quantitated. Considerable differences were found for some constructs if tested in vitro or in vivo. From the data obtained, a set of expression vectors for basic research as weH as for aquaculture purposes were established.},
  subject      = {Schwertk{\"a}rpfling},
  language  = {en}
}
@article{WinklerVielkindSchartl1991,
  author    = {Winkler, Christoph and Vielkind, J{\"u}rgen R. and Schartl, Manfred},
  title     = {Transient expression of foreign DNA during embryonic and larval development of the medaka fish (Oryzias latipes)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61743},
  year      = {1991},
  abstract  = {Species of small fish are becoming useful tools for studies on vertebrate development. Wehave investigated the developing embryo of the Japanese medaka for its application as a transient expression system for the in vivo analysis of gene regulation and function. The temporaland spatial expression patterns ofbacterial chloramphenicol acetyltransferase and galactosidase reporter genes injected in supercoiled plasmid form into the cytoplasm of one cell of the two-cell stage embryo was promoter-specific. The transient expression was found to be mosaic within the tissue and organs reflecting the unequal distribution of extrachromosomal foreign DNA and the intensive cell mixing movements that occur in fish embryogenesis. The expression data are consistent with data on DNA fate. Foreign DNA persisted during embryogenesis and was still detectable in some 3- and 9-month-old adult fish; it was found in high molecular weight form as weil as in circular plasmid conformations. The DNA was replicated during early and late embryogenesis. Our data indicate that the developing medaka embryo is a powerful in vivo assay system for studies of gene regulation and function.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WinklerWittbrodtLammersetal.1994,
  author    = {Winkler, Christoph and Wittbrodt, Joachim and Lammers, Reiner and Ullrich, Axel and Schartl, Manfred},
  title     = {Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87107},
  year      = {1994},
  abstract  = {Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales.},
  subject      = {Japank{\"a}rpfling},
  language  = {en}
}
@article{WittbrodtAdamMalitscheketal.1989,
  author    = {Wittbrodt, J. and Adam, D. and Malitschek, B. and Maueler, W. and Raulf, F. and Telling, A. and Robertson, M. and Schartl, Manfred},
  title     = {Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61800},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WittbrodtLammersMalitscheketal.1992,
  author    = {Wittbrodt, Joachim and Lammers, Reiner and Malitschek, Barbara and Ullrich, Axel and Schartl, Manfred},
  title     = {Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61699},
  year      = {1992},
  abstract  = {Xmrk encodes a putative transmembrane glycoprotein of the tyrosine kinase family and is a melanoma-inducing gene in Xiphophorus. We attempted to investigate the biological function of the putative Xmrk receptor by characterizing its signalling properties. Since a potential Iigand for Xmrk has not yet been identified, it has been difficult to analyse the biochemical properlies and biological function of this cell surface protein. In an approach towards such analyses, the Xmrk extracellular domain was replaced by the closely related Iigand-binding domain sequences of the human epidennal growth factor receptor (HER) and the ligand-induced activity of the chimeric HER-Xmrk proteinwas examined. We show that the Xmrk protein is a functional receptor tyrosine kinase, is highly active in malignant melanoma and displays a constitutive autophosphorylation activity possibly due to an activating mutation in its extracellular or transmembrane domain. In the focus formation assay the HER-Xmrk chimera is a potent transfonning protein equivalent to other tyrosine kinase oncoproteins.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{YanHongChenetal.2013,
  author    = {Yan, Yan and Hong, Ni and Chen, Tiansheng and Li, Mingyou and Wang, Tiansu and Guan, Guijun and Qiao, Yongkang and Chen, Songlin and Schartl, Manfred and Li, Chang-Ming and Hong, Yunhan},
  title     = {p53 Gene Targeting by Homologous Recombination in Fish ES Cells},
  series = {PLoS One},
  volume    = {8},
  journal   = {PLoS One},
  number    = {3},
  doi       = {10.1371/journal.pone.0059400},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133416},
  pages     = {e59400},
  year      = {2013},
  abstract  = {Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7\%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5\%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6\% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.},
  language  = {en}
}