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

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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.