Worm Breeder's Gazette 11(5): 92

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.

Dominant Suppressors of glp-1(e2142)

Ann Marie Howell and James R. Priess

We are interested in identifying genes whose products interact with 
glp-1 during embryogenesis.  Our approach has been to identify and 
characterize mutations which suppress the temperature sensitive 
maternal effect embryonic lethal phenotype of glp-1(e2142).  EMS-
induced suppressors of glp-1(e2142), (called sog), have been isolated 
in a screen which demanded that the suppressors be dominant sog 
alleles of genes which were expressed in the germ line.  L1 larvae 
from glp-1(e2142); permissive temperature 
were mutagenized and shifted up to restrictive temperature.  Offspring 
would hatch and grow only if a suppressor mutation had been induced, 
since glp-1(e2142) produces no viable embryos at 25 C.  If the sog 
mutation had occurred in the soma of the hermaphrodite parent, the 
suppression would not be heritable in the surviving progeny.  However, 
if the sog had occurred in one of the two germ line progenitor cells, 
the suppression would be heritable.
The EMS-induced suppressors define three sog loci.  Eight of these 
suppressors map to two loci on LGI, and 30 are linked to LGIII.  One 
of the sog loci on LGI is extremely close to the left of dpy-5, and 
the other is between unc-29 and unc-75.  The sog locus on LGIII was 
positioned approximately halfway between unc-79 and dpy-17.  These 
suppressors only suppress the e2142 allele of glp-1.Surprisingly, we 
recovered dominant suppressors at a frequency expected for loss of 
function mutations.  If these were loss of function mutations, we 
anticipated that we might be able to isolate additional sog alleles 
from a strain which would generate transposable element induced 
mutations.  Both dominant and recessive suppressors were isolated from 
glp-1(e2142); unc-22.  The dominant suppressors 
are likely to be allelic with the loci identified by the EMS-induced 
mutations, however their dominance precludes simple tests for 
complementation.  One dominant mutator-induced sog on LGIII has been 
isolated.  It maps to the same region as the EMS-induced sog.  Of 
thirteen dominant suppressors on LGI, eleven map close to dpy-5 and 
two map to the right.  Ten of the eleven alleles are associated with 
an apparent Tc1 insertion in the region to the left of dpy-5.Another 
way to test the hypothesis that these are loss of function alleles is 
to see how they behave in strains with different ratios of mutant and 
wild-type alleles.  hDp20 has been used to supply an extra wild-type 
allele of the sog locus close to dpy-5.  sog/sog suppresses twice as 
well as +/sog.  +/sog/sog suppresses with a similar efficiency to 
+/sog, but +/+/sog shows almost no suppression.  A deficiency which 
includes this locus, sDf4, suppresses glp-1(e2142) indicating that 
simply reducing the amount of the sog(+) product suppresses glp-1(
e2142).  We asked whether increasing the amount of the sog(+) product 
would exacerbate the glp-1(e2142) defect.  We find that a strain with 
three copies of sog(+) produces mostly Glp embryos at a temperature 
normally permissive for growth.
The suppressed strains appear wild-type.  We removed glp-1(e2142) 
from the suppressor strains to determine whether the suppressors had 
any other phenotype.  A mutator-induced allele of each of the three 
loci was tested.  The Sog mutant strains have no visible phenotype and 
have normal levels of embryonic viability and fertility.  It is 
possible that these genes are functionally redundant members of a gene 
family, so we are constructing strains with multiple sog mutations to 
look for a phenotype.  A Sog double mutant strain containing both of 
the LGI sogs also has no phenotype.  We are currently constructing a 
Sog triple mutant strain.