PAX 7 ist ein Gen mit, neben anderen Funktionen, ausgeprägter neuroentwicklungsgeschichtlicher Bedeutung. Schizophrenie wird heute als primär genetisch bedingte Neuroentwicklungstörung aufgefaßt (I.1.2, Abbildung 2). Im Rahmen dieser Dissertation wurde die Assoziation zwischen den drei repetitiven Trinukleotidpolymorphismen vom (CCT)n Typ und ihren fünf korrespondierenden Genotypen in der regulatorischen Sequenz der PAX 7 Promotorregion, die bekannterweise die Expressionshöhe des PAX 7 Genproduktes beeinflussen und einer Prädisposition zur Entwicklung einer Schizophrenie oder einer Ihrer Subkategorien nach DSM-IV3 (paranoid, nicht-paranoid, schizoaffektiv) mittels eines Polymerasekettenreaktions-basierten Assays in Proben von 280 an Schizophrenie erkrankten Patienten und 229 Kontrollproben gesunder Blutspender untersucht. Weder auf der genotypischen noch auf der allelischen Ebene konnte eine statistisch signifikante Korrelation nachgewiesen werden. Die PAX 7 Promotor Polymorphismen stellen also keine nützlichen Biomarker einer schizophren Polymorphismen Prädisposition dar. Die Rolle dieser Polymorphismen in anderen PAX 7 abhängigen Mechanismen bedarf weiterer Aufklärung, während polygen orientierte „Komplettgenom“ Techniken (z.B. genexpression profiling) besser geeignet sein könnten um das multifaktorielle Netz der Schizophrenie-Entwicklung aufzuklären. / Pax 7 is a gene of , among other features, enormous neurodevelopmental importance. Schizophrenia is today considered to be a primarily genetic based neurodevelopmental disease (I.1.2, figure 2). In this thesis the association between the three repetitive trinucleotide polymorphisms of the (CCT)n type and their five existing genotypic expressions, known to affect expression levels of Pax 7, in the regulative sequence of the Pax 7 promotor and the predisposition towards development of schizophrenia or its subcategories according to DSM-IV3 (paranoid, not-paranoid, schizoaffective) was analyzed by means of an polymerase chain reaction based assay in the DNA of 280 pts. afflicted by this condition and 229 control samples from healthy blood donors. No statistical association was found neither on the genotypic nor the allelic level. Thus Pax 7 promotor polymorphisms are no usefull biomarkers of a predisposition towards a development of schizophrenic manifestations. The role this polymorphisms in other Pax 7 related mechanisms should be further elucidated, while polygenic oriented whole genome techniques (e.g. genexpression profiling) seem to be candidates to entangle the multifactorial web of schizophrenic predisposition.

This study investigates the skeletal muscle repair and regeneration process following blunt trauma injury in murine models. Skeletal muscle injury is recorded most often in sports injuries and include strains and sprains, contusions, and bruising, however, there is growing consensus about the role skeletal muscle plays in the reparative process of bone fractures. Skeletal muscle stem cells or satellite cells are mesenchymal stem cell derived cells that exist between the basal lamina and cell membrane of muscle fibers usually in close proximity to capillary beds. After a traumatic injury, satellite cells respond to the influx of signaling from immune cells, oxygen tension, and myogenic proteins which influence differentiation into myoblasts for repair of tissue damage. Research continues to elucidate the relationship between bone and skeletal muscle following trauma injuries. Skeletal muscle stem cells play a vital role in fracture healing, and in certain conditions, are even induced into the osteogenic pathway. The goals of this study are to characterize the temporal progression of myogenesis during muscle repair that will be used with future studies of muscle and bone injury. And to identify potential crosstalk mechanisms between muscle and bone repair during trauma. In our experiment model trauma was introduced to mice with a modified muscle contusion device where a weight was dropped onto the femoral quadriceps muscles and the quadriceps and biceps muscle tissues were harvested at post-operative days (POD) 2, 4, 12, 16, and 24. Reverse-Transcriptase Quantitative Polymerase Chain Reaction was used to analyze gene expression profiles for satellite/stem cells (Pax7 and Prx1), muscle regeneration (MyoD, Myf5, Myl2, and Myh1), angiogenesis (VegfA, VegfR2), myokine (Myostatin and IL6), and BMP signaling (ID1). Our findings indicate that both Pax7 and Prx1 expression slightly decreased after injury but showed a significant (p<0.05) increase and peak of expression at POD 16 in the femoral quadriceps muscles. The early myogenic genes, MyoD and Myf5 peaked early at POD 4 while the adult myofiber markers, Myl2 and Myh2, peaked later at POD 16 in the femoral quadriceps muscles. Only slight changes were observed in the femoral biceps muscles. The angiogenic genes peaked at POD16 in the femoral quadriceps muscles and POD 12 in the femoral biceps muscles. The expression of Myostatin, an inhibitor of muscle mass, decreased early (POD 4 and 12) however showed a non-significant increase at POD 16 in the femoral quadriceps muscles. Lastly, the expression of ID1, which is downstream target of BMP signaling peaked early at POD 4 in the femoral quadriceps muscles. These data indicates that stem/satellite cells decrease in response to muscle injury but by POD 4, myogenic commitment and programming occurs. While early myogensis occurs, BMP signaling peaks and Myostatin expression decreases suggesting a coordinated event. Adult myofiber regeneration occurs in parallel to angiogenesis. The myogenic events were primarily isolated to the injured femoral quadriceps muscles. This model of muscle injury can be used to study muscle regeneration within context to bone injury.