Differentially expressed cortical genes contribute to perivascular deposition in transgenic mice with inducible neuron-specific expression of TGF-β1

Abstract

In the brain the expression of transforming growth factor β1 (TGF-β1) is involved both in neuroprotective and neurodegenerative processes. Recently, we have established a transgenic mouse model with inducible neuron-specific expression of TGF-β1 based on the tetracycline-regulated gene expression system. A long-term expression of TGF-β1 results in persisting perivascular thioflavin-positive depositions, which did not disappear even though the transgene synthesis was repressed completely by administration of doxycycline. Formation and composition of these depositions are hardly elucidated. The aim of this study was to identify TGF-β1 responding genes potentially participating in forming these depositions. To address this problem we have compared the cortical mRNA expression pattern of TGF-β1 expressing mice with mice impeded to express the transgenic protein using oligonucleotide microarray analysis. Differential gene expression was further characterized by quantitative real-time reverse transcription-polymerase chain reaction including animals, where the long-lasting TGF-β1 expression was repressed. While no change of amyloid precursor protein RNA expression level was detected, various genes strongly involved in calcium homeostasis, tissue mineralization or vascular calcification were identified differentially expressed. It is suggested, that these genes might contribute to the perivascular depositions in the TGF-β1 expressing mice.