The normal function of the dunce+ gene of Drosophila melanogaster is required for normal memory processes, since flies carrying a mutant version of the gene exhibit abbreviated memories of conditioned behaviors. This gene has been isolated from the fly and our recent studies conclusively demonstrate that the gene codes for the enzyme, cyclic AMP phosphodiesterase. This indicates that the enzyme and its substrate, cyclic AMP, play a central role in the biochemical processes underlying memory. Recently, we have isolated a clone from a rat genomic library (named rat dunce-1) by hybridization to the Drosophila dunce+ gene and partial sequence analysis demonstrates that it is probably the rat homolog of the Drosophila dunce+ gene. We propose here to gather additional preliminary information about this gene and other rat genes homologous to Drosophila dunce+ to guide us into long-term studies of these genes. The rat dunce-1 clone will be used to probe the RNA populations of various rat tissues to determine where the gene is expressed and to gain information about the number and sizes of homologous RNAs. The clone will then be used to select clones from cDNA libraries made from rat brain RNA or RNA of other tissues. In addition, other rat sequences which are homologous to the Drosophila dunce+ clone will be selected from a genomic library and these will be partially sequenced, to determine if these also contain phosphodiesterase genes. These pilot studies will position us to determine (1) the structural organization of the rat phosphodiesterase genes and their modes of regulation, (2) the degree of evolutionary conservation with Drosophila dunce+, and (30 whether the mammalian phosphodiesterase genes participate in memory processes like the dunce+ gene of flies.
| Davis, R L; Takayasu, H; Eberwine, M et al. (1989) Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene. Proc Natl Acad Sci U S A 86:3604-8 |
