title: Steel-Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains.
abstract: Mice homozygous for the viable Sl allele steel-Dickie (Sld) are sterile, severely anemic, and black-eyed white. The nature of the Sld mutation was investigated at the molecular level and was found to be due to a 4.0-kilobase intragenic deletion in mast cell growth factor (MGF) genomic sequences, providing conclusive evidence that Sl encodes MGF. As a consequence of this deletion, Sld is only capable of encoding a soluble truncated growth factor that lacks both transmembrane and cytoplasmic domains. Northern analysis indicates that Sld mRNA is expressed at approximately wild-type levels in adult tissues, and yeast expression studies suggest that the Sld protein is as biologically active as wild-type soluble MGF. These studies provide a molecular basis for explaining the Sld phenotype, a description of a germ-line mutation in the transmembrane and cytoplasmic domains of a membrane-bound growth factor, and in vivo evidence for the importance of membrane-bound forms of growth factors in mammalian development.
authors.affiliation: Mammalian Genetics Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
authors.forename: C I
authors.initials: CI
authors.lastname: Brannan
authors.forename: S D
authors.initials: SD
authors.lastname: Lyman
authors.forename: D E
authors.initials: DE
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Eisenman
authors.forename: D M
authors.initials: DM
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Cosman
authors.forename: M A
authors.initials: MA
authors.lastname: Bedell
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002462:Cell Membrane / Q000502:physiology; D002872:Chromosome Deletion; D003593:Cytoplasm / Q000502:physiology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D015183:Restriction Mapping
chemical_list: D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit