TY - JOUR A1 - Winkler, Christoph A1 - Wittbrodt, Joachim A1 - Lammers, Reiner A1 - Ullrich, Axel A1 - Schartl, Manfred T1 - Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene N2 - 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. KW - Japankärpfling KW - Ligand KW - Tumor Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87107 ER - TY - JOUR A1 - Winkler, Christoph A1 - Hong, Yunhan A1 - Wittbrodt, Joachim A1 - Schartl, Manfred T1 - Analysis of heterologous and homologous promoters and enhancers in vitro and in vivo by gene transfer into Japanese medaka (Oryzias latipes) and Xiphophorus N2 - 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. KW - Schwertkärpfling KW - Japankärpfling KW - Gentransfer KW - Enhancer KW - Promotor KW - In vitro KW - In vivo Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86796 ER - TY - JOUR A1 - Foerster, Wolfgang A1 - Schartl, Manfred T1 - Karyotype and isozyme patterns of five species of Aulonocara REGAN, 1922 N2 - No abstract available. KW - Aulonocara KW - Karyotyp KW - Isoenzym Y1 - 1987 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86774 ER - TY - JOUR A1 - Hannig, Gerhard A1 - Ottilie, Sabine A1 - Schartl, Manfred T1 - Conservation of structure and expression of the c-yes and fyn genes in lower vertebrates N2 - The src-gene family in mammals and birds consists of 9 closely related protein tyrosine kinases. We have cloned the c-yes and fyn bomologues of the src-family from the teleost fish Xiphophorus helleri. Both genes show a high degree of sequence conservation and exhibit all structural motifs diagnostic for functional src-like protein tyrosine kinases. Sequence comparisons revealed three domains (exon 2, exons 3--6, exons 7-12) which evolve at different rates. Both genes exhibit an identical expression pattern, with preferential expression in neural tissues. No transcripts of c-yes were found in liver wbich is contrary to the situation in higher vertebrales. In malignant melanoma, elevated Ieveis of c-yes andfyn were detected indicating a possible function during secondary steps of tumor progression for src-related tyrosine kinases. KW - Konservierung KW - Gen KW - Niedere Wirbeltiere Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86723 ER - TY - JOUR A1 - Raulf, Friedrich A1 - Mäueler, Winfried A1 - Robertson, Scott M. A1 - Schartl, Manfred T1 - Localization of cellular src mRNA during development and in the differentiated bipolar neurons of the adult neural retina in Xiphophorus N2 - The expression of the c-src gene in embryonie and adult tissue of the teleost fish Xiphophorus helleri was analyzed by in-situ hybridization. The highly conserved fish c-src gene was found to be expressed at high levels in midterm embryos, where c-src mRNA was localized in developing neurons of the sensory layer of the differentiating retina and in the developing brain. In adult tissues the expression of c-src was found to persist in certain cell types of the brain and the neural retina, especially in the bipolar cells of the inner nuclear layer, which are postmitotic, fully differentiated mature neurons. Thus c-src in Xiphophorus appears to be a developmentally regulated proto-oncogene which is important for neuronal differentiation during organogenesis, but whose persistence of expression in certain terminally differentiated neurons strongly suggests a particular maintenance function for c-src in these cells as well. KW - Schwertkärpfling KW - Messenger-RNS Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86703 ER - TY - JOUR A1 - Barnekow, Angelika A1 - Jahn, Reinhard A1 - Schartl, Manfred T1 - Synaptophysin: a substrate for the protein tyrosine kinase pp60c-src in intact synaptic vesicles N2 - Expression of pp60 c-src, the first well defined proto-oncogene product, is developmentally regulated and tissue-specific, with neuronal tissues displaying high amounts of the c-src encoded pp60 c-src kinase activity. In the central nervous system pp60 s-src is preferentially expressed in regions characterized by a high content of grey matter and elevated density of nerve terminals. In this study we show for the first time a direct interaction between pp60 c-src and synaptophysin as a physiological target protein in neurons by demonstrating that endogenous pp60 c-src is able to phosphorylate synaptophysin (p38). p38 is a major constituent of the synaptic vesicle membrane protein and is thought to play a key role in the exocytosis of small synaptic vesicles and possibly small clear vesicles in neuroendocrine cells. KW - Synaptophysin KW - Synaptische Vesikel KW - Protein-Tyrosin-Kinasen Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86168 ER - TY - JOUR A1 - Schartl, A. A1 - Schartl, Manfred A1 - Anders, F. T1 - Promotion and regression of neoplasia by testosterone-promoted cell differentiation in Xiphophorus and Girardinus N2 - No abstract available. KW - Schwertkärpfling KW - Lebendgebärende Zahnkarpfen Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86684 ER - TY - CHAP A1 - Schreibman, Martin P. A1 - Schartl, Manfred A1 - Kallman, Klaus D. A1 - Magliulo-Cepriano, Lucia T1 - Molecular approaches to study the genetic regulation of the fish reproductive system N2 - No abstract available. KW - Fische Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86679 ER - TY - CHAP A1 - Schartl, A. A1 - Schartl, Manfred A1 - Anders, F. T1 - Phenotypic conversion of malignant melanoma to benign melanoma and vice versa in Xiphophorus N2 - No abstract available. KW - Schwertkärpfling KW - Krebs Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86662 ER - TY - CHAP A1 - Anders, F. A1 - Scholl, E. A1 - Schartl, Manfred T1 - Environmental and hereditary factors in the causation of neoplasia, based on studies of the Xiphophorus fish melanoma system N2 - Neoplasia in Xiphophorus can be classified into: a) a Jarge group triggered by carcinogens; b) a large group triggered by promoters; and c) a small group that develops "spontaneously" according to Mendelian Jaw. The process leading to susceptibility for neoplasia is represented by the disintegration of gene systems that normally protect the fish from neoplasia. Interpopulational arid interracial hybridization is the most effective process that Ieads to disintegration of the protective gene systems. Environmental factors may complete disintegration in somatic cells and thus may trigger neoplasia. The applications of the findings on Xiphophorus to humans are discussed. KW - Schwertkärpfling KW - Gen KW - Umweltfaktor KW - Tumor Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86402 ER -