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Genetics, Vol 142, 935-944, Copyright © 1996
INVESTIGATIONS |
Deletion and Interallelic Complementation Analysis of Steel Mutant Mice
M. A. Bedell, L. S. Cleveland, T. N. O'Sullivan, N. G. Copeland and N. A. Jenkins
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201
Mutations at the Steel (St) locus produce pleiotropic effects on viability as well as hematopoiesis, pigmentation and fertility. Several homozygous viable Sl alleles have previously been shown to contain either structural alterations in mast cell growth factor (Mgf) or regulatory mutations that affect expression of the Mgf gene. More severe Sl alleles cause lethality to homozygous embryos and all lethal Sl alleles examined to data contain deletions that remove the entire Mgf coding region. As the timing of the lethality varies from early to late in gestation, it is possible that some deletions may affect other closely linked genes in addition to Mgf. We have analyzed the extent of deleted sequences in seven homozygous lethal Sl alleles. The results of this analysis suggest that late gestation lethality represents the Sl null phenotype and that peri-implantation lethality results from the deletion of at least one essential gene that maps proximal to Sl. We have also examined gene dosage effects of Sl by comparing the phenotypes of mice homozygous and hemizygous for each of four viable Sl alleles. Lastly, we show that certain combinations of the viable Sl alleles exhibit interallelic complementation. Possible mechanisms by which such complementation could occur are discussed.
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