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.

Pharmacological Characterization and Cloning of kra-1 Mutant

Hideki Ando and Hiroaki Kagawa

Figure 1

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 
[See Figure 1]

Figure 1