Worm Breeder's Gazette 11(1): 47
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
We have previously reported on isolation of ketamine response abnormal (KRA) mutants by temporary convulsive phenotypes (WBG vol10, No.3, 1988 and CSH 1989). Ketamine, a general anesthetic, is one of the non-competitive antagonist of N-methyl-D-aspartate (NMDA). Genetic and molecular study on genes that have influence on normal pharmacological response to such drugs must be an adequate approach to understanding the NMDA class of glutamate receptor. As reported previously, we identified a gene, kra-1 on LGV by genetic study on a strain kh-30. Genetic locus of kh-30 mutation site was determined between right side breakpoints of nDf32 and sDf20 (0.08mu in span). This mutation expresses a semidominant convulsive phenotype in 30mM ketamine solution or other NMDA antagonists, a strong inhibition of postembryonic development of 10mM ketamine containing NGA, a recessive cold sensitive Unc phenotype, and variable motility in usual condition. As suggested by John White, we also tested previously isolated strains including 26 unc loci derived from over 30 genes and some levamisole resistant strains appeared to be blocked their postembryonic development by ketamine. In addition, some mutant that have abnormal neuron networks showed ketamine resistance in postembryonic development. On the other hand, in immediate response to ketamine, hypersensitive paralyzing strains (whole body and head region restricted) could be found. We are observing pharmacological responses of KRA and other strains to acetylcholine antagonists or other reagents. Pharmacological and anatomical data will give us any suggestions about the ketamine functional site on neuron networks in the worm. Tc1 tagging of mec-1 gene is in progress with generous supply of Tc1 clones by Marty Chalfie. We do hope mec-1 linked fragment will be cloned for matching physical map and genetic map very soon. [See Figure 1]