The W(sh) and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in W(sh) and Ph mutant mice Academic Article uri icon


MeSH Major

  • Chromosome Mapping
  • Embryo, Mammalian
  • Gene Expression
  • Mice, Inbred C57BL
  • Mutation
  • Proto-Oncogene Proteins
  • Proto-Oncogenes
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Colony-Stimulating Factor
  • Receptors, Platelet-Derived Growth Factor


  • The receptor tyrosine kinases (RTKs) c-kit and platelet-derived growth factor receptor alpha chain (PDG-FRa) are encoded at the white spotting (W) and patch (Ph) loci on mouse chromosome 5. While W mutations affect melanogenesis, gametogenesis, and hematopoiesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. W-sash (Wsh) is an expression mutation and blocks c-kit expression in certain cell types and enhances c-kit expression in others, including at sites important for early melanogenesis. We have determined the effect of Ph on c-kit expression during embryogenesis in Ph heterozygotes. Immunohistochemical analysis revealed enhanced c-kit expression in several cell types, including sites important for early melanogenesis. We propose that in both Wsh and Ph mutant mice c-kit misexpression affects early melanogenesis and is responsible for the pigment deficiency. Moreover, we have defined the organization of the RTKs in the W/Ph region on chromosome 5 and characterized the Wsh mutation by using pulsed-field gel electrophoresis. Whereas the order of the RTK genes was determined as Pdgfra-c-kit-flk1, analysis of the Wsh mutation revealed that the c-kit and Pdgfra genes are unlinked in Wsh, presumably because of an inversion of a small segment of chromosome 5. The Ph mutation consists of a deletion including Pdgfra and the 3' deletion endpoint of Ph lies between Pdgfra and c-kit. Therefore, positive 5' upstream elements controlling c-kit expression in mast cells and some other cell types are affected by the Wsh mutation and negative elements are affected by both the Wsh and the Ph mutation.

publication date

  • January 1995



  • Academic Article



  • eng

PubMed Central ID

  • PMC42040

PubMed ID

  • 7537375

Additional Document Info

start page

  • 3754

end page

  • 8


  • 92


  • 9