Gene Dmel\dnc

Gene encodes a cAMP-specific phosphodiesterase. Mutants blocked or impaired in learning, with respect to several of the conditioning tests used on groups of flies or larvae or on individual adults, e.g., those involving odors and electric shocks or sugars (Aceves-Pina and Quinn, 1979, Science 206: 93-96; Tempel, Bonini, Dawson, and Quinn, 1983, Proc. Nat. Acad. Sci. USA 80: 1482-86; see also Aceves-Pina, Booker, Duerr, Livingstone, Quinn, Smith, Sziber, Tempel, and Tully, 1983, Cold Spring Harbor Symp. Quant. Biol. 48: 831-40), visual stimuli (Folkers, 1982, J. Insect Physiol. 28: 535-39), or various elements of courtship (with respect to tests on mutant males or females, summarized by Hall, 1984, Dev. Genet. 4: 355-78); also, dncM14 males have reduced reproductive fitness after exposure to and courtship of immature females, i.e. when mutant males are put, post training, with mixed female/young male populations (Gailey, Siegel, and Hall, 1985, Genetics 111: 795-804). dnc females display an increased frequency of mating; it is suggested that this could account for their 50% normal longevity (Bellen and Kiger, 1987, Genetics 115: 153-60). dnc males are not conditioned to avoid virgin females by sequestration with such females in the presence of quinine; wild type males are (Ackerman and Siegel, 1986, J. Neurogenet. 3: 111-23). dnc mutants apparently learn normally, or nearly so, in certain experiments but have abnormally short memory (e.g., Dudai, 1979, J. Comp. Physiol. 130: 271-75; Mariath, 1985, J. Insect Physiol. 31: 779-87); more specifically, modificatons of original shock-odor testing system reveal that dnc is defective in short term memory, with long-term memory similar to wild type (Tully and Quinn, 1985, J. Comp. Physiol. 157: 263-77); dnc/+ females also memory deficient (Dudai, 1983, Proc. Nat. Acad. Sci. USA 80: 5445-48). Whereas dnc adults seem normal in several general behaviors (Dudai et al., 1976), the mutant displays aberrant "centrophobic" behavior [i.e., transient avoidance of the center of an arena displayed by normal adults (Gotz and Biesinger, 1985, J. Comp. Physiol. 156: 319-27, 329-37)]. Mosaic studies suggest that the focus of dnc/+ function is the brain, even though some learning responses demonstrated by headless flies (Aceves-Pina, et al.). Sensory fatigue associated with an adult mechanosensory neuron, as measured by bristle stimulation, occurs more rapidly than normal in dnc (allele not specified) (Corfas and Dudai, 1990, J. Neurosci. 10: 491-99). There is an increased number of mushroom-body axonal fibers in young adults expressing dnc1 or dncM11, which, unlike wild type, decreases over the next few days (Balling, Technau, and Heisenberg, 1987, J. Neurogenet. 4: 65-73). Mutations or deletions of the locus reduce or eliminate one form of cyclic AMP phosphodiesterase (EC 3.1.4.17) activity; caffeine, an inhibitor of this enzyme, decreases visual learning performance of normal adults and of dnc1 as well, suggesting that the biochemical effects of the drug and the mutation are not identical (Folkers and Spatz, 1984, J. Insect Physiol. 30: 957-65). The effects of dnc mutations on heat stability or Km of this activity indicate that the locus codes for this enzyme (Kauvar, 1982, J. Neurosci. 2: 1347-58; Davis and Kauvar); dnc variants also lead to increased levels of cyclic AMP (summarized by Davis and Kauvar, 1983), more specifically, such that most of the excess is in free (vs. bound) nucleotide; both fractions exist in whole-fly homogenates (Friedrich, Solti, Gyurkovicz, 1984, J. Cell. Biochem. 26: 197-203). dncM11 affects the level of phosphorylation of the regulatory subunit of the cyclic-AMP-dependent kinase (Devay, Pinter, Yalcin, and Friedrich, 1986, Neurosci. 18: 193-203). Levels of regulatory subunit of cAMP-dependent protein kinase tend to be higher than normal in dnc1 and dnc2 (Muller and Spatz, 1989, J. Neurogenet. 6: 95-114). dncM11 flies exhibit increased levels of expression of copia (Yun and Davis, 1989, Nucleic Acids Res. 17: 8313-26). dnc alleles cause varying degrees of female sterility; oocytes of females homozygous for amorphic alleles rarely reach maturity, and for the most part are not oviposited; 90% of the few that are oviposited are fragile, lacking a chorion. That this phenotype is somatic in origin is demonstrated by the observation that homozygous germ-line clones produce morphologically normal eggs; some of these eggs undergo a few abortive nuclear divisions, but they never reach an identifiable stage of oogenesis. The maternal-effect lethality partially suppressible by rut, which reduces adenylate cyclase activity. The earliest defect seen in the embryos produced by dnc rut females occurs soon after fertilization and affects DNA replication and mitosis, prevents nuclear migration, and leads to large polyploid nuclei; a later defect prevents cleavage nuclei from migrating into, or dividing in, the poserior region of the egg, affecting the developmental behavior or fate of blastoderm cells. The few surviving offspring of double-mutant females show frequent developmental abnormalities of the second and third thoracic, and the first five abdominal segments; these include deficiencies, duplications, and transformation of structures; some 15% of the daughters of such females lack one or both ovaries (Livingstone, Sziber, and Quinn, 1984, Cell 37: 205-15; Bellen, Gregory, Olsson, and Kiger, 1987, Dev. Biol. 121: 432-44; Bellen and Kiger, 1988, Roux's Arch. Dev. Biol. 197: 258-68).