DEVELOPMENTAL REGULATION OF THE NERVE GROWTH FACTOR RECEPTOR GENE

神经系统中的细胞存活和分化是由 许多多肽生长因子，其中神经生长因子（NGF）具有 提供了最令人信服的证据， 发展 神经生长因子与两种不同的反应神经元相互作用 受体分子，低亲和力（p75NGFR）NGF受体和 原癌基因trk的产物p140trk。 虽然这两 受体被认为参与介导神经营养作用 并在应答细胞上共表达， 这些神经生长因子受体基因还不清楚。 我们打算利用基因 转移技术和转基因小鼠来确定DNA元件 p75NGFR和p140trk两者的适当神经元表达所需。 NGF的生物学作用可能取决于适当的 调节和化学计量的两种受体在正确的细胞 类型 因此，这些研究将使我们了解 神经系统中神经营养作用的分子要求， 并将为神经退行性疾病的研究提供新的方向 如帕金森氏症和阿尔茨海默氏痴呆症。

Cell survival and differentiation in the nervous system are mediated by many polypeptide growth factors, of which nerve growth factor (NGF) has provided the most compelling evidence for a physiological role during development. NGF interacts on responsive neurons with two different receptor molecules, the low affinity (p75NGFR) NGF receptor and the product of the proto-oncogene trk, p140trk. Although these two receptors are believed to be involved in mediating neurotrophic effects and to be coexpressed on responsive cells, regulation of expression of these NGF receptor genes is not understood. We intend to use gene transfer techniques and transgenic mice to define the DNA elements required for proper, neuronal expression of both p75NGFR and p140trk. NGF's biological actions are likely to depend upon appropriate regulation and stoichiometry of the two receptors in the correct cell types. Therefore, these studies will allow us to understand the molecular requirements for neurotrophic action in the nervous system, and will suggest new directions for studying neurodegenerative diseases such as Parkinson's and Alzheimer's dementia.