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AuthorSchreiber, Sabinedc.contributor.author
Date of accession2019-02-11T10:07:22Zdc.date.accessioned
Available in OPARU since2019-02-11T10:07:22Zdc.date.available
Year of creation2018dc.date.created
Date of first publication2019-02-11dc.date.issued
AbstractCardiovascular diseases are the leading cause of death worldwide. Changes in chromatin structure alter gene expression and drive cardiovascular disease pathogenesis. The SET ((Su(var)3-9), enhancer of zeste (E(z)) and trithorax (Trx)) domain-containing protein family is such a group of chromatin modifiers, who are known to methylate histones. The SET domain-containing protein 5 (setd5) is a member of this family and was previously connected to cardiovascular disease generation in mouse. The purpose of the presented thesis was to further characterize the role of Setd5 in vertebrate heart development. Since embryonic mice are not viable without a functional cardiovascular system, the zebrafish was chosen as a model organism because of its ease of genetic manipulation and the ability to survive without a functional cardiovascular system. Setd5 deficiency, generated by Morpholino-modified antisense oligonucleotide injection in zebrafish embryos, resulted in severe cardiac defects. Although no impairment in heart differentiation and specification was evident, the observed heart morphology was highly altered. Atria appeared stretched and thin, whereas the ventricle presented a compact and lumpy conformation. Functional analysis showed that Setd5 is essential to maintain cardiac contractile function in zebrafish. Loss of Setd5 led to a distinct phenotype, mainly a silent ventricle and atrial arrhythmia. Analysis of the cardiac conduction system showed regular excitation propagation in the atrium and dysfunctional electrical excitation of ventricular cardiomyocytes. Focusing on chromatin modification, knockdown of setd5 led to increased methylation and reduced acetylation of histones. In conclusion, loss of setd5 impairs cardiac morphology and function in vivo.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (ohne Print-on-Demand)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_opod_v1dc.rights.uri
KeywordSetd5dc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHImmunoglobulin domainsdc.subject.mesh
MeSHZebrafishdc.subject.mesh
MeSHAtrial fibrillationdc.subject.mesh
MeSHMorpholinosdc.subject.mesh
MeSHCardiovascular diseases; Pathologydc.subject.mesh
TitleTargeted loss of SET domain-containing protein 5 impairs cardiac morphology and function in vivodc.title
Resource typeDissertationdc.type
Date of acceptance2019-01-11dcterms.dateAccepted
RefereeJust, Steffendc.contributor.referee
RefereeWeishaupt, Jochendc.contributor.referee
DOIhttp://dx.doi.org/10.18725/OPARU-11862dc.identifier.doi
PPN1655078194dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-11919-4dc.identifier.urn
GNDZebrabärblingdc.subject.gnd
GNDFibrillationdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionUKU. Klinik für Innere Medizin IIuulm.affiliationSpecific
InstitutionUKU. Klinik für Neurologieuulm.affiliationSpecific
Grantor of degreeMedizinische Fakultätuulm.thesisGrantor
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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