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-32的表达、结构和功能 ARPP-16。我们将描述大鼠的cDNA，当与 牛序列，将使我们能够检测到高度保守的区域 可能的生理意义。这些探头也将被用来研究 药物处理的大鼠体内特异的mRNA值。我们还将 鉴定这些蛋白质的人类cDNA，这些探针将是 用于研究基底节疾病患者的样本， 以及在分子遗传学方面的应用。我们将分离小鼠的基因组 用于细胞表达研究的ARPP-19/16的克隆，并获得 启动子区域，将用于在转基因小鼠中直接表达。 这些小鼠将被用于生理和生化研究。最后， 这些DNA将被用来产生突变形式的蛋白质，用于 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.