Gene Dmel\para

Exposure to 29-30 causes rapid paralysis that is quickly reversed on shift to 22-25. Larvae are paralyzed, too, at somewhat higher temperatures. Flies of some para strains seem sluggish at lower temperatures. When these mutants are still paralyzed (i.e. at high temperatures), they appear to retain many of their "vital functions," their heart still beats (Grigliatti, Suzuki and Williamson, 1972), and they quickly regain normal behavior when shifted to 22 after several hours at 29 (Suzuki et al., 1971); in fact, after a less prolonged exposure (30 min) to high temperature, the still-heated mutant flies regain weak mobility and are even able to right themselves and walk (Suzuki et al, 1971). parats/+ adults become paralyzed at 40 within one min [10 min required to paralyze wild-type (Hall, 1973, DIS 50: 103-04)]. parats1 larvae stop "tracking" at high temperature (Wu, Ganetzky, Jan, Jan and Benzer, 1978, Proc. Nat. Acad. Sci. USA 75: 4047-51). parats1 is nearly unconditionally lethal when uncovered by a deletion or other para-locus aberration, whereas other alleles lead to reduced viability (unconditional) when heterozygous with chromosomal aberrations at the locus (Ganetzky, 1984). Action potentials in larval nerves are reversibly heat-sensitive (Wu and Ganetzky, 1980), and the same can be inferred for at least some adult neurons (indicated by brain stimulation and recording of responses in thoracic muscles [Siddiqi and Benzer, 1976, Proc. Nat. Acad. Sci. USA 73: 3253-57; Benshalom and Dagan, 1981, J. Comp. Physiol. 144: 409-17]). Other "excitable phenomena," such as the electroretinogram responses and synaptic transmission, appear to be normal in parats adults at high temperature (Suzuki et al., 1971; Siddiqi and Benzer, 1976); also parats1 does not block action potentials in the cervical giant fiber at high temperature (Nelson and Baird, 1985, Neurosci. Abstr. 11: 313) in contrast to results of recording from larval motor neurons (Wu and Ganetzky, 1980); other studies of the giant fiber pathway (involving adult mosaics bilaterally split, externally, for parats1 and para+) indicate that at least certain elements of the pathway (if not the giant fiber itself) fail to fire action potentials at elevated temperature (Benshalom and Dagan, 1981), and recordings from mosaics of this type also suggest "functional coupling" between left and homologous right sides of this giant fiber pathway (Benshalom and Dagan, 1985, J. Comp. Physiol. 156: 13-23). parats1 causes first larval instar death when in combination with napts (Wu and Ganetzky, 1980; Ganetzky, 1984); similar lethality occurs when para+ dosage is decreased in a napts background (Ganetzky, 1984). Other para alleles, in combination with napts, lead to reduced viability, with parats115 having the strongest effect, followed by paraST76 and paraST109 (Ganetzky, 1984). In combination with the tipE mutation, para mutations again cause decreased viability, but the allele-specific interactions are different from those of the series just noted [i.e. with respect to napts (Ganetzky, 1986)]. Surviving para; tipE double mutants are weak, and show accentuated heat-sensitivity (in regard to mobility and nerve conduction); para alleles are dominant for behavioral defects in a homozygous tipE background (Ganetzky, 1985). In adults doubly mutant for parats1 and napts, sensory cells (developing from imaginal discs in mosaics) appear to have no nerve conduction (Burg and Wu, 1984, Neurosci. Abstr. 10: 513). In mosaics involving para mutations only one allele (paraST109) causes all legs to be either paralyzed or normal in different individual gynandromorphs (Siddiqi and Benzer), in contrast to independent paralysis of legs in mosaics constructed with respect to parats1 [Grigliatti et al., 1972; Siddiqi and Benzer, 1978, Genetic Mosaics and Cell Differentiation (Gehring, ed.). Springer-Verlag, Berlin, pp: 259-305]. These results (and others, Benshalom and Dagan, 1985, for example), reveal poor correlation of the externally mutant genotype (in mosaics) and behavioral or physiological malfunctions [consistent with internal (no doubt neural) "foci" for para's action]. In other studies, parats1 mosaics with mutant heads (scored externally) usually are immobile at high temperature, but maintain normal posture (Suzuki et al., 1971; Grigliatti et al., 1972). Exposure of parats1 males to high temperature causes arrest of the oscillator underlying rhythmic component of courtship song (Kyriacou and Hall, 1985). At permissive temperatures, parats1 neurons (unlike those influenced by napts) seem normal, except that there is slightly increased resistance of cultured parats1 larval neurons to killing effects of veratridine, shift to high temperature causing that resistance to increase (Suzuki and Wu, 1984, J. Neurogenet. 1: 225-38). Other pharmacological studies (tetrodotoxin sensitivity of action potentials or binding assays involving that toxin) have revealed no para-induced abnormalities (Ganetzky and Wu, 1980; Kauvar, 1982, Molec. Gen. Genet. 187: 172-73). It was reported (based on injection of parats1 adults with picrotoxin and the ensuing inhibition of paralysis at high temperatures) that the mutation is involved in a generalized augmentation of inhibition mediated by gamma-amino-butyric acid [Williamson, Kaplan and Dagan, 1974, Nature (London) 252: 224-26] but further physiological data (involving administration of picrotoxin) dispute this hypothesis. parats1 is reported to cause an anomalous inflection point in Arrhenius plots, with respect to activity of the mitochondrial enzyme succinate cytochrome c reductase, at a temperature close to that which induces paralysis (Søndergaard, 1976, Hereditas 82: 51-56).

Responds poorly, or apparently not at all, to a variety of volatile compounds; hence, may be generally olfaction defective, as opposed to responding poorly to only certain classes of synthetic or natural compounds; sbl1 was isolated with respect to abnormal shock-avoidance learning tests of adults, which involve odor cues (Aceves-Pina and Quinn, 1979); sbl2 was isolated with regard to odor response tests per se (Rodrigues and Siddiqi, 1978); sbl1 and sbl2 defective in larval olfaction (Aceves-Pina and Quinn, 1979; Monte et al., 1989) and fail to complement in this regard (Lilly and Carlson, 1990); the latter report showed sbl2 to respond poorly to 3 separate odorants; both of these mutants also behave subnormally in tests of larval contact chemosensory responses, but each is normal in visually mediated larval behavior (Lilly and Carlson, 1990); sbl1 and sbl2 are temperature-sensitive near-lethals in 29 rearing tests, and they fail to complement in this regard (Lilly and Carlson, 1990); a post eclosion shift from 25 to the higher temperature does not appear to affect viability, but adults under these conditions have not been tested behaviorally--recall that sbl2 flies are defective in odor responses (Rodrigues and Siddiqi, 1978; Gailey et al., 1986), and sbl1 adults are as well (Aceves-Pina and Quinn, 1979; Tompkins et al., 1980; J. Carlson, unpublished--the latter determination used testing procedures as reported by Woodward, Huang, Sun, Helfand, and Carlson, 1989, Genetics 123: 315-326). Other alleles are unconditionally lethal. In courtship experiments, sbl1 (Tompkins et al., 1980) or sbl2 (Gailey et al., 1986) males make little or no responses to pheromonal materials extracted from adult females; the former mutant, as a male, also performs subnormally in terms of quantitative measurements of overall courtship interactions with females (Tompkins et al., 1980) as well as by specification of individual elements of such sexual behavior (Markow, 1987). seemingly as a consequence, sbl1 males exhibit mediocre mating success (Tompkins et al., 1980; Markow, 1987); the latter is observed when the mutant males are with females only (Tompkins et al., 1982) or are also in competition with wild-type males (Markow, 1987). sbl2 males are rather wild-type-like, with respect to short-term monitoring of their behavior in presence of females and also in terms of mating success (Gailey et al., 1986); a sbl2 male, however, makes almost no odor-mediated responses to a courtship object in his presence, as stimulated by a female placed nearby, whereas wild-type males are rather vigorously stimulated to court under these circumstances (Gailey et al., 1986). Females homozygous for sbl1 (Tompkins et al., 1982; Markow, 1987) or sbl2 (Gailey et al., 1986) exhibit relatively poor receptivity to male courtship/mating activities; this could be explained by the fact that they tend not to slow their movements in response to the courting male, whereas wild-type females do (Tompkins et al., 1982; Gailey et al., 1986). Courtship-experience-dependent after-effects, which appear to be in part mediated olfactorily, are subnormal or absent in tests of sbl1 males with fertilized females (Tompkins et al., 1983). In experiments involving counts of post-eclosion mushroom-body fiber (axon) numbers in young imagoes, deantennated vs. intact sbl1 flies were found to exhibit same degree of reductions in fiber numbers (Technau, 1984)--suggesting that deantennation, which leads to such decreases in wild-type adults, effects these anatomical changes because of sensory deprivation, instead of surgery-induced injury per se.