Beschreibung
Studies on humans already showed enamel and bone defects connected to peroxisomal biogenesis disorders. Nevertheless, there are no microscopic investigations about the effects of peroxisomal disorders on teeth and alveolar bone yet. The present dissertation expanded the symptoms of peroxisomal biogenesis disorders through morphological and cellbiological analysis of dental and alveolar bone tissues. The peroxisomal compartiment in dental cells and its significance for odontogenesis was further characterized. Earlier results of our research group could show that peroxisomes play an important role in odontogenesis when it comes to secretory ameloblasts and odontoblasts and therefore defects in enamel and dentin in mice with peroxisomal biogenesis disorder were likely. For the characterization of these defects the Pex11-knockout mouse model and corresponding wildtype and heterozygotes, which were formaldehyd-fixed and paraffin-embedded were used in this dissertation. The Pex11-knockout mouse model was described as very suitable to investigate peroxisomal biogenesis disorders in different organs (e.g. ZNS). For the characterization of defects newborn mice of the different Pex11-genotypes were fixed with 4% Paraformaldehyde-PBS-solution and paraffin-embedded. With the help of immunofluorescence using specific markers it was possible to describe the effects of the Pex11-knockout on tooth development precisely. Both peroxisomal monospecific markers such as catalse, PEX14p, PEX13p, PEX3p, PEX19p, PEX5p and mitochondrial markers such as SOD2 and complex IV of the respiratory chain (OxPhos) were used. Moreover also cytoskeletal markers, which are important for the differentiation of ameloblasts and odontoblasts and bone-specific markers such as osteocalcin and osteopontin for the investigation of alveolar bone and odontoblasts were used. The results of this dissertation demonstrated that the peroxisomal compartiment was very prominent in secretory ameloblasts and odontoblasts and therefore might be important for the formation of enamel and dentin. The results revealed furthermore a clear decrease of peroxisomes in the molars of the Pex11-knockout mice. This was particulary evident in the ameloblasts, whereat the decreased presence of amelogenin and connexin 43 could explain the observed hypomineralization of enamel in patients with diseases of the Zellweger syndrome spectrum. Furthermore the mineralizationmarkers of dentin and alveolar bone were reduced in the Pex11-knockout mice, which indicates a hypomineralization in these mice. Whereas the hypomineralization of enamel was already described in patients with peroxisomal disorders, the hypomineralization of dentin so far has never been described before in the international literature. The Pex11-heterozygous mice also showed defects in enamel, dentin and alveolar bone, but they were not that severe and mostly not statistically significant. It also was confirmed for dental tissues what was previously demonstrated for several other tissues, namely that peroxisomal defects have an impact on mitochondrial activity. The Pex11-knockout mouse model turned out to be very suitable to characterize the molecular pathogenesis in dental tissues associated with peroxisomal disorders.
