0000000000132887

AUTHOR

T. Hankeln

Transgene Tiere in Forschung, Medizin und Landwirtschaft

Obwohl es schon seit Anfang der 70er Jahre moglich war, Gene in Mikroorganismen und Zellkulturzellen zu uberfuhren („klassische“ Gentechnik), dauerte es weitere 10 Jahre, bevor es gelang, auch vielzellige Organismen gezielt gentechnisch zu verandern. Bei vielzelligen Tieren ist nicht nur die Vielzelligkeit ein Problem, sondern auch die Existenz einer sog. Keimbahn. Die Keimbahn ist die Generationsfolge einer besonderen Zellpopulation, die ausschlieslich fur die Bildung der Keimzellen von Tieren verantwortlich ist. Nur die Keim(bahn)zellen geben ihre genetische Information an die nachste Generation weiter. Daraus folgt, das eine gezielte gentechnische Veranderung eines Tieres, wenn sie uber …

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When the brain goes diving: glial oxidative metabolism may confer hypoxia tolerance to the seal brain.

Deep diving mammals have developed strategies to cope with limited oxygen availability when submerged. These adaptations are associated with an increased neuronal hypoxia tolerance. Brain neurons of the hooded seal Cysto- phora cristata remain much longer active in hypoxic condi- tions than those of mice. To understand the cellular basis of neuronal hypoxia tolerance, we studied neuroglobin and cy- tochrome c in C. cristata brain. Neuroglobin, a respiratory protein typically found in vertebrate neurons, displays three unique amino acid substitutions in hooded seal. However, these substitutions unlikely contribute to a modulation of O2 affinity. Moreover, there is no significant difference i…

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In situlocalization of the evolutionary conserved Cpy/Cty gene in the subfamily Chironominae (Chironomidae, Diptera): establishment of chromosomal homologies

The homologous sites on the salivary gland chromosomes of 13 species from three genera: Chironomus, Glyptotendipes, Kiefferulus have been mapped by means of fluorescent in situ hybridization using the evolutionary conserved gene Cpy⁄Cty (clone Cla1.1). In all species of genus Chironomus and genus Kiefferulus, the Cty⁄Cpy gene is located on arm F of chromosome EF. The relocation of the gene among the species of genus Chironomus can be done by simple or complex homozygous inversions which occurred during the divergent evolution of the chromosome of the species. In the genus Glyptotendipes, the Cty⁄Cpy gene was localized in arm E of chromosome EF. Since the banding patterns of salivary gland c…

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From critters to cancers: bridging comparative and clinical research on oxygen sensing, HIF signaling, and adaptations towards hypoxia

The objective of this symposium at the First International Congress of Respiratory Biology (ICRB) was to enhance communication between comparative biologists and cancer researchers working on O(2) sensing via the HIF pathway. Representatives from both camps came together on August 13-16, 2006, in Bonn, Germany, to discuss molecular adaptations that occur after cells have been challenged by a reduced (hypoxia) or completely absent (anoxia) supply of oxygen. This brief "critters-to-cancer" survey discusses current projects and new directions aimed at improving understanding of hypoxic signaling and developing therapeutic interventions.

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Untersuchungen zum Gentransfer und zur Freisetzung von DNA aus trangenen Pflanzen

Die Moglichkeiten der Ausbreitung von Transgenen durch sexuellen oder horizontalen Gentransfer wurden am Beispiel von Freilandversuchen mit Herbizid-resistentem Raps in Rheinland-Pfalz untersucht. In Abhangigkeit von Klimaund Wetterbedingungen sowie der Grose der Anbauflache kann beim Raps eine Auskreuzung transgener DNA auf nicht-transgenem Raps oder verwandte Wildformen stattfinden. Die Raps-DNA (und damit auch daspat-Gen) persistiert uber Monate hinweg im Boden und steht damit prinzipiell fur eine Aufnahme durch Mikroorganismen zur Verfugung. Eine haufige Integration in das Genom von Bakterien oder gar die Realisierung der aufgenommenen genetischen Information ist jedoch wenig wahrschein…

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The amphibian globin gene repertoire as revealed by the <i>Xenopus </i>genome

The draft genome sequence of the Western clawed frog <i>Xenopus (Silurana) tropicalis</i> facilitates the identification, expression analysis and phylogenetic classification of the amphibian globin gene repertoire. Frog and mammalian neuroglobin display about 67% protein sequence identity, with the expected predominant expression in frog brain and eye. Frog and mammalian cytoglobins share about 69% of their amino acids, but the frog protein lacks the mammalian-type extension at the C-terminus. Like in mammals, <i>X. tropicalis</i> cytoglobin is expressed in many organs including neural tissue. Neuroglobin and cytoglobin genomic regions are syntenically conserved in a…

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Interspecies comparison of neuroglobin, cytoglobin and myoglobin: Sequence evolution and candidate regulatory elements

Neuroglobin and cytoglobin are two novel members of the vertebrate globin family. Their physiological role is poorly understood, although both proteins bind oxygen reversibly and may be involved in cellular oxygen homeostasis. Here we investigate the selective constraints on coding and non-coding sequences of the neuroglobin and cytoglobin genes in human, mouse, rat and fish. Neuroglobin and cytoglobin are highly conserved, displaying very low levels of non-synonymous nucleotide substitutions. An oxygen supply function predicts distinct modes of gene regulation, involving hypoxia-responsive transcription factors. To detect conserved candidate regulatory elements, we compared the neuroglobin…

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Protection of islets in culture by delivery of oxygen binding neuroglobin via protein transduction.

Islet transplantation has become an accepted method to treat type 1 diabetes. To succeed and achieve normal levels of glucose in transplant recipients, the quality of the transplanted islets is of the utmost importance. Lack of oxygen during organ procurement, islet isolation, and subsequent culture triggers apoptosis or necrosis and loss of islet function, causing the yield and quality to diminish. A promising candidate for cytoprotection against oxygen deprivation is neuroglobin (Ngb). Ngb is a recently described member of globin family and is expressed in neurons, retina, and pancreatic islets. To overexpress this protein in the islets and study its ability to protect them, we utilized p…

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Oxygen binding properties of non-mammalian nerve globins

Oxygen-binding globins occur in the nervous systems of both invertebrates and vertebrates. While the function of invertebrate nerve haemoglobins as oxygen stores that extend neural excitability under hypoxia has been convincingly demonstrated, the physiological role of vertebrate neuroglobins is less well understood. Here we provide a detailed analysis of the oxygenation characteristics of nerve haemoglobins from an annelid (Aphrodite aculeata), a nemertean (Cerebratulus lacteus) and a bivalve (Spisula solidissima) and of neuroglobin from zebrafish (Danio rerio). The functional differences have been related to haem coordination: the haem is pentacoordinate (as in human haemoglobin and myogl…

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