Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice

Genes Dev. 1989 Jun;3(6):816-26. doi: 10.1101/gad.3.6.816.

Abstract

The proto-oncogene c-kit, a transmembrane tyrosine protein kinase receptor for an unknown ligand, was shown recently to map to the dominant white spotting locus (W) of the mouse. Mutations at the W locus affect various aspects of hematopoiesis, as well as the proliferation and/or migration of primordial germ cells and melanoblasts during development. Here, we show that c-kit is expressed in tissues known to be affected by W mutations in fetal and adult erythropoietic tissues, mast cells, and neural-crest-derived melanocytes. We demonstrate that the c-kit associated tyrosine-specific protein kinase is functionally impaired in W/WV mast cells, thus providing a molecular basis for understanding the developmental defects that result from these mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Anemia, Macrocytic / enzymology
  • Anemia, Macrocytic / genetics*
  • Animals
  • Cell Movement
  • Embryonic and Fetal Development
  • Genes, Lethal
  • Hematopoiesis
  • Hematopoietic Stem Cells / enzymology
  • Heterozygote
  • Liver / embryology
  • Liver / enzymology
  • Mast Cells / enzymology
  • Melanocytes / enzymology
  • Melanoma, Experimental
  • Mice
  • Mice, Mutant Strains / embryology
  • Mice, Mutant Strains / genetics*
  • Mice, Mutant Strains / metabolism
  • Neural Crest / pathology
  • Organ Specificity
  • Pigmentation Disorders / embryology
  • Pigmentation Disorders / enzymology
  • Pigmentation Disorders / genetics*
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogenes*
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured / enzymology

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit