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Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1

Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1


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MANGERICH, Aswin, Nadja HERBACH, Benjamin HANF, Arthur FISCHBACH, Oliver POPP, Maria MORENO-VILLANUEVA, Oliver T. BRUNS, Alexander BÜRKLE, 2010. Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1. In: Mechanisms of Ageing and Development. 131(6), pp. 389-404. ISSN 0047-6374. eISSN 1872-6216

@article{Mangerich2010Infla-8204, title={Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1}, year={2010}, doi={10.1016/j.mad.2010.05.005}, number={6}, volume={131}, issn={0047-6374}, journal={Mechanisms of Ageing and Development}, pages={389--404}, author={Mangerich, Aswin and Herbach, Nadja and Hanf, Benjamin and Fischbach, Arthur and Popp, Oliver and Moreno-Villanueva, Maria and Bruns, Oliver T. and Bürkle, Alexander} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/8204"> <dc:contributor>Bruns, Oliver T.</dc:contributor> <dc:creator>Bruns, Oliver T.</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8204"/> <dc:format>application/pdf</dc:format> <dc:creator>Fischbach, Arthur</dc:creator> <dc:creator>Herbach, Nadja</dc:creator> <dc:contributor>Fischbach, Arthur</dc:contributor> <dc:contributor>Moreno-Villanueva, Maria</dc:contributor> <dc:contributor>Hanf, Benjamin</dc:contributor> <dc:language>eng</dc:language> <dc:creator>Mangerich, Aswin</dc:creator> <dc:creator>Bürkle, Alexander</dc:creator> <dc:contributor>Popp, Oliver</dc:contributor> <dc:contributor>Herbach, Nadja</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:41:24Z</dc:date> <dc:rights>deposit-license</dc:rights> <dc:creator>Popp, Oliver</dc:creator> <dc:creator>Hanf, Benjamin</dc:creator> <dcterms:abstract xml:lang="eng">Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD+ serving as substrate. PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death. Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor. Recently, we generated a mouse model with ectopic integration of full-length hPARP-1 [Mangerich, A., Scherthan, H., Diefenbach, J., Kloz, U., van der Hoeven, F., Beneke, S. and Bürkle, A., 2009. A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1. Transgenic Res. 18, 261 279]. Here, we show that hPARP-1 mice exhibit impaired survival rates accompanied by reduced hair growth and premature development of several inflammation and age-associated pathologies, such as adiposity, kyphosis, nephropathy, dermatitis, pneumonitis, cardiomyopathy, hepatitis, and anemia. Moreover, mutant male mice showed impaired glucose tolerance, yet without developing manifest diabetes. Overall tumor burden was comparable in wild-type and hPARP-1 mice, but tumor spectrum was shifted in mutant mice, showing lower incidence of sarcomas, but increased incidence of carcinomas. Furthermore, DNA repair was delayed in splenocytes of hPARP-1 mice, and gene expression of pro-inflammatory cytokines was dysregulated. Our results suggest that in hPARP-1 mice impaired DNA repair, accompanied by a continuous low-level increase in pro-inflammatory stimuli, causes development of chronic diseases leading to impaired survival.</dcterms:abstract> <dcterms:title>Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1</dcterms:title> <dcterms:bibliographicCitation>First publ. in: Mechanisms of Ageing and Development 131 (2010), 6, pp. 389-404</dcterms:bibliographicCitation> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-06-30T22:25:04Z</dcterms:available> <dc:contributor>Bürkle, Alexander</dc:contributor> <dcterms:issued>2010</dcterms:issued> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> <dc:contributor>Mangerich, Aswin</dc:contributor> <dc:creator>Moreno-Villanueva, Maria</dc:creator> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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