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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Anemia, Macrocytic / enzymology
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Anemia, Macrocytic / genetics*
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Animals
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Cell Movement
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Embryonic and Fetal Development
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Genes, Lethal
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Hematopoiesis
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Hematopoietic Stem Cells / enzymology
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Heterozygote
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Liver / embryology
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Liver / enzymology
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Mast Cells / enzymology
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Melanocytes / enzymology
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Melanoma, Experimental
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Mice
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Mice, Mutant Strains / embryology
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Mice, Mutant Strains / genetics*
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Mice, Mutant Strains / metabolism
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Neural Crest / pathology
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Organ Specificity
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Pigmentation Disorders / embryology
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Pigmentation Disorders / enzymology
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Pigmentation Disorders / genetics*
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / genetics*
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-kit
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Proto-Oncogenes*
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RNA, Messenger / analysis
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Tumor Cells, Cultured / enzymology
Substances
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Proto-Oncogene Proteins
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RNA, Messenger
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-kit