Guillemot Fabrice, Cerutti Italina, Auffray Charles, Devignes Marie-Dominique
Genexpress, Génomique Fonctionnelle et Biologie Systémique pour la Santé, CNRS et Université Pierre et Marie Curie Paris VI, LGN, UMR 7091, 7 rue Guy Moquet, BP8, 94801 Villejuif, France.
Transgenic Res. 2007 Apr;16(2):223-37. doi: 10.1007/s11248-006-9060-0. Epub 2007 Jan 16.
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.
脑源性神经营养因子（BDNF）是治疗各种神经退行性疾病（如阿尔茨海默病或帕金森病）的一个有吸引力的成分。创新的非侵入性治疗方法涉及在大脑中适当药理诱导内源性BDNF合成。已建立一种转基因小鼠模型来研究人BDNF基因表达，并允许筛选能够刺激其活性的化合物。携带人BDNF基因的145kb酵母人工染色体已被改造以产生转基因，该转基因包含扩展的BDNF启动子和3'侧翼区域，并已将增强型绿色荧光蛋白（E-GFP）编码序列整合到BDNF编码外显子的位置。通过将酵母人工染色体显微注射到受精小鼠卵母细胞中获得了五个转基因品系。从三个表达转基因的品系中，有一个显示出BDNF表达的特定模式。报道了BDNF 5'外显子的忠实组织限制性转录以及荧光报告基因产物在预期脑区的定位。该品系构成了一个可用于体内研究人BDNF基因调控的系统。
