Abstract
Brain-derived neurotrophic factor (BDNF) is an attractive component for the treatment of various neurodegenerative diseases such as Alzheimer's or Parkinson's disease. Innovative non-invasive therapeutic approaches involve appropriate pharmacological induction of endogenous BDNF synthesis in brain. A transgenic mouse model has been established to study human BDNF gene expression and permit the screening of compounds capable of stimulating its activity. A 145-kb yeast artificial chromosome carrying the human BDNF gene has been engineered to produce the transgene which contains the extended BDNF promoter and 3' flanking regions and has integrated the enhanced green fluorescent protein (E-GFP) coding sequence in place of the BDNF coding exon. Five transgenic lines have been obtained through microinjection of the YAC into fertilized mouse oocytes. From the three lines expressing the transgene, one displays the specific pattern of BDNF expression. Faithful tissue-restricted transcription of BDNF 5' exons and localization of the fluorescent reporter gene product in the expected brain subregions are reported. This line constitutes an exploitable system for investigating human BDNF gene regulation in vivo.
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