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AuthorDiebold, Ruthdc.contributor.author
Date of accession2016-03-14T13:39:44Zdc.date.accessioned
Available in OPARU since2016-03-14T13:39:44Zdc.date.available
Year of creation2007dc.date.created
AbstractNeurofibromatosis type 2 (NF2) is a highly penetrant, autosomal dominantly inherited disorder. The affected individuals show a predisposition for tumors in the central and the peripheral nervous system. The classical hallmarks are bilateral vestibular schwannomas. NF2 is caused by inactivating mutations in a gene on the chromosome 22q12, which is coding for the protein merlin. The protein shares sequence and function similarity to the ERM proteins and also acts as a molecular linker between the cytoskeleton and the plasma membrane. But only merlin can function as a negative growth regulator. Therefore it is thought to be a tumor suppressor protein. According to this each patient inherits one mutation in the germline found in every cells. Tumor formation follows the inactivation of the remaining wild-type allele. Beside the locally found tumors the NF2 patient often shows a distal symmetric neuropathy, that in most cases cannot be explained as a burder of spinal tumors or toumorlets around peripheral nerves at sites of bonal foramina. Additionally Schwann cells in sural nerve biopsies show abnormalities. The genotype of these cells is so far unknown. Since the increasing evidence of other tumor suppressor genes, haploinsufficiency can give rise to diseases that are related but different from diseases following the complete loss of both alleles. To find out if the second hit has already taken place or merlin shows haploinsufficiency, the gene dosage in peripheral nerve biopsies of patients with neuropathy should be analysed. Therefore a multiplex dosage-PCR assay was established to screen the NF2 gene for the deletion of one or more exons in DNA extracted from paraffin sections. To verify this finding a cell culture model was established. In a mesothelioma cell line, expressing merlin, the expression of the NF2 gene was reduced to a dosage of approximately 50 % using shRNA expressing constructs and the expression of several selected proteins and genes was identified.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 03.05.2003)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v1dc.rights.uri
KeywordGene dosage PCRdc.subject
KeywordHaploinsuffizienzdc.subject
KeywordNeurofibromatose Typ 2dc.subject
KeywordNF2dc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
MeSHNeurofibromatosis 2dc.subject.mesh
TitleUntersuchungen zur Haploinsuffizienz im Neurofibromatose Typ 2 Gendc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-500dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-59290dc.identifier.urn
GNDPolyneuropathiedc.subject.gnd
FacultyFakultät für Naturwissenschaftenuulm.affiliationGeneral
Date of activation2007-06-18T17:41:32Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 11.471 ; W: W-H 9.589uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID5929uulm.vtsID
CategoryPublikationenuulm.category


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