Worm Breeder's Gazette 11(2): 93
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.
DNA sequence analysis suggests that lin-12 and glp-1 encode homologous transmembrane receptor proteins (1,2). Despite the similarity of the putative lin-12 and glp-1 gene products, the phenotype of a loss of function mutation in either gene is unique. glp-1(q231)lf has a strict maternal effect lethal phenotype and a zygotic effect germ line proliferation defect (1). lin-12(q269)lf causes zygotic effect transformations in cell fate in several different lineages (1, T. Schedl, pers. comm.). A lin-12(q269) homozygote will usually mature into a sterile or subfertile adult with a protruding vulva; however, a small percentage of worms with this genotype arrest as moribund L1s. These arrested worms are characterized by several morphological abnormalities, most obviously the absence of a rectum. The double mutant, lin-12(q269) 1), invariably arrests as an L1, resembling that produced at low frequency by the single mutation, lin-12(q269). The synergistic effect of the lin-12 and glp-1 mutations indicates that the wild type glp-1 gene product substitutes (or otherwise compensates) for the loss of lin-12 function. The distinctive nature of the highly penetrant L1 lethal phenotype observed in the lin-12 utant (designated here as 'Lag' for phenotype of mutations in both lin-12 and alp-1) has provided us with a means of identifying mutations in genes that are required for the function of both lin-12 and glp-1. From approximately 4500 EMS mutagenized F1 clones, we have identified seven recessive mutations that result in the Lag phenotype. Three of these map to a single locus, lag-1, situated between the clusters on chromosome IV. Four mutations map to the left arm of chromosome V. Three of these are moderately linked to dpy-11, and may be alleles of the same gene, lag-2. In addition to mapping in the same vicinity, each of these three mutations exhibits a temperature sensitivity: at 15 C a fraction of the homozygous worms mature into sterile adults with a germ line phenotype identical to that produced by mutations in glp-1. The remaining mutation on chromosome V is located more distally, closer to unc-34 than dpy-11, and has been tentatively designated as an allele of lag-3. Complementation analysis will soon establish the allelism of the different mutations on V. Additional phenotypic and genetic analyses will be necessary to establish the roles of the lag genes in the normal functioning of lin- 12 and glp-1.*E.L. is supported by grant DRG 989 from the Damon Runyon-Walter Winchell Cancer Fund.