MOLECULAR BIOLOGY OF BASAL GANGLIA-SPECIFIC PHOSPHOPROTEINS(RAT,MICE,HUMAN,CATTLE

我们建议使用重组DNA技术来进一步研究 DARPP-32、ARPP-21、ARPP- 19和 ARPP- 16我们将描述大鼠cDNA的特征，当与 牛的序列，将使我们能够检测高度保守的区域， 可能的生理意义。这些探针也将用于研究 特异性mRNA水平。我们还将 表征这些蛋白质的人类cDNA，这些探针将被 用于基底神经节疾病患者样品的研究， 以及分子遗传学应用。我们将分离出老鼠的基因组 用于细胞表达研究的ARPP-19/16的克隆，并获得 启动子区域，其将用于指导转基因小鼠中的表达。 这些小鼠将用于生理和生化研究。最后， cDNA将用于产生蛋白质的诱变形式， 生化研究。

We propose to use recombinant DNA techniques to further our studies of the expression, structure, and function of DARPP-32, ARPP-21, ARPP- 19, and ARPP- 16. We will characterize the rat cDNAs, which, when compared to the bovine sequences, will allow us to detect highly conserved regions of probable physiologic significance. These probes will also be used to study specific mRNA levels in pharmacologically manipulated rats. We will also characterize the human cDNAs for these proteins, and these probes will be utilized in studies of samples from patients with basal ganglia diseases, and in molecular genetic applications. We will isolate the mouse genomic clone for ARPP-19/16 for use in cell-expression studies, and to obtain a promotor region which will be used to direct expression in transgenic mice. These mice will be used for physiological and biochemical studies. Finally, the cDNAs will be used to produce mutagenized forms of the protein for biochemical studies.