Molekulare Charakterisierung transgener Mauslinien mit deregulierter IKK2 Funktion in Neuronen

Abstract

Only little is known about the function of NF-kB in the central nervous system (CNS). To study the role of NF-kB in neurons mutants of the IKK2 have been expressed in transgenic mice using a tet-off-system. A dominant-negative (IKK2-DN) and a constitutive-active (IKK2-CA) version of the IKK protein have been used. Before this study have been performed an analysis of the weight and size of the mice, experiments with Doxycyclin administration to determine the exact time point for the development of the phenotype and a genechip analysis. The analysis of the weight and size showed a phenotype of reduced weight and size of the IKK2-DN +/+ mice. Through the Doxycyclin administration day E 16.5 to E 18.5 could be estimated to be crucial for the development of the phenotype. The genechip analysis brought up five differentially regulated candidate genes all with unknown function. The aim of this study was to characterize this mouse model biomolecularly. The focus was to study the reason for the phenotype of the IKK2-DN +/+ mice. Therefore we analyzed the mRNA expression of genes, related to metabolism, neuron development or known correlation with NF-kB, in different regions of the brain. The main focus was on genes of the growth hormone system and the regulation of energy homeostasis in the brain. In summary, this work gives a new insight into the biomolecular changes caused by neuronal modulation of the IKK activity in transgenic mice and provides a contribution to the understanding of the function of NF-kappa B in neurons.