Worm Breeder's Gazette 12(3): 31 (June 15, 1992)
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.
sdc-1 is an X-linked gene required for the hermaphrodite modes of dosage compensation and sex determination in C. elegans. XX sdc-1 mutants are dumpy, egglaying defective, have elevated X-linked transcript levels, and exhibit an incompletely penetrant transformation towards the male fate. XO animals are phenotypically wild type. The fact that sdc-1 mutations affect both dosage compensation and sex determination indicates that sdc-1 acts at a point prior to the divergence of the sex determination and the dosage compensation pathways. sdc-1 acts as a negative regulator of the her-1 sex determination gene, which is required for male development and is transcriptionally regulated. The sdc-1 gene encodes a 1203 amino acid protein with seven zinc finger motifs in the N-terminal portion. No similarities have been found for the C-terminal portion of the protein.
We have molecularly characterized thirteen of the nineteen sdc-1 alleles in order to establish the null phenotype and to discern the role of the zinc fingers. Of these mutations, n485 and y146 are identical nonsense mutations that eliminate 90% of the protein and all of the zinc finger motifs. Animals homozygous for these alleles are Dpy and exhibit a weak (<1%) sexually transformed phenotype, the null phenotypes. y64 and e2497 are donor splice site mutations in an intron that occurs in the middle of the sixth zinc finger. Nine of the thirteen remaining characterized alleles are clustered and alter the protein after the seven zinc fingers, suggesting the existence of a domain critical for sdc-1 function. y67 changes a gly to a glu towards the C-terminus of the protein. This allele is temperature sensitive and causes the most sexually transformed phenotype of the genetically characterized alleles (30% incomplete males at 20°C). The other eight alleles contain stop codons or small out-of-frame deletions (2 to 4 bases). These alleles are similarly deficient in dosage compensation but display variable degrees of sexual transformation.
To clarify whether the zinc fingers are truly required for sdc-1 function, we used site-directed mutagenesis to knock out various combinations of these zinc fingers. We are now testing these mutant genes for their ability to rescue the dosage compensation and sex determination defects of n485 in germ line transformation experiments.