Steel-Dickie mutation encodes a c-kit ligand lacking transmembrane and cytoplasmic domains.

作者：Camilynn I. Brannan, Stewart D. Lyman, Douglas E. Williams, June Eisenman, Dirk M. Anderson, David J. Cosman, Mary A. Bedell, N.A. Jenkins, Neil G. Copeland · 发表于：Proceedings of the National Academy of Sciences · 年份：1991 · DOI：10.1073/pnas.88.11.4671 · 被引用次数：303 · 研究领域：Mast cells and histamine、Kruppel-like factors research、Cell Adhesion Molecules Research

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.