Worm Breeder's Gazette 15(4): 23 (October 1, 1998)

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.

The dim-1 gene encodes a novel protein required for myofilament stability and unc-112 encodes a homolog of the human MIG-2 protein

Teresa Rogalski, Mary Gilbert, Danelle Devenport, Don Moerman

Department of Zoology, University of British Columbia, Vancouver, B.C. Canada

     Embryos homozygous for null mutations in the unc-112 gene exhibit a
Pat terminal phenotype.  They arrest at the two-fold stage of
embryogenesis and have severely disorganized body wall muscle (Williams
and Waterston, 1994, JCB 124:475-490).  In contrast, animals carrying
the r367 allele are viable, although they do have severely disorganized
body wall muscle and are paralyzed as adults.  We have isolated several
extragenic suppressors of  unc-112(r367) by selecting well moving anmals
from the progeny of mutagenized hermaphrodites.  All of the suppressor
mutations characterized are alleles of  the dim-1 (disorganized muscle)
gene which we have positioned  between dpy-7 and dpy-6 on the X
chromosome.  These alleles are null mutations and are able to suppress
the paralyzed phenotype of  unc-112(r367) when either heterozygous (good
suppression) or homozygous (better suppression).  Thus, reduction or
loss of  dim-1 gene function results in suppression of  unc-112(r367).  
Hermaphrodites homozygous for a dim-1 mutation on its own appear
wild-type under the dissecting microscope.  However, the body wall
muscle is easily disrupted and appears disorganized when viewed under
polarized light.
     The dim-1 gene corresponds to the C18A11.7 and C18A11.8 open
reading frames identified by the C. elegans sequencing consortium. 
Although identified by Genefinder as two separate genes, sequencing of
the cDNA clone YK399b7 obtained from Y. Kohara revealed that these ORFs
are part of a single gene consisting of 12(?) exons with a rather large
(3.5 kb) intron separating exons 6 and 7.  We have identified the
sequence alterations for three of the dim-1 alleles.  One (ra111) is a
183  bp deletion that extends from the middle of exon 8 into the
adjacent downstream intron, and the two remaining mutations (ra209 and
ra114) delete the 3' end of the gene.  The dim-1 gene encodes a novel
640 amino acid protein that is presumably required for myofilament
lattice stability in the body wall muscle.  The first 315 amino acids of
this protein (encoded by exons 1 through 6) are not similar to any known
protein whereas the remaining 325 amino acids constitute three
immunoglobulin repeats similar to those found in Titin and
     The unc-112 gene maps to the left of unc-76 on LG V in the interval
between the left breakpoints of the deficiencies, yDf9 and yDf11.  We
have rescued the mutant phenotype of  unc-112(r367) with a 7.5 kb
fragment subcloned from one of the cosmids in this region  containing
the C47E8.7 ORF plus 2.5 kb of upstream sequence.  The C47E8.7( unc-112)
gene encodes a 720 amino acid protein that is most similar to a human
protein of unknown function called MIG-2 (J. Cell Sci. 107:227).  A full
length cDNA (YK12c6) obtained from Y. Kohara has been sequenced and the
results confirm the gene structure predicted by Genefinder.  This
putative UNC-112 protein shares a short, ~50 amino acid region of
homology with Talin, Band 4.1 and Ezrin which may be important for
attaching these proteins to the plasma membrane.