Expression of functional c-kit receptors rescues the genetic defect of W mutant mast cells

EMBO J. 1991 Dec;10(12):3683-91.

Abstract

Loss-of-function mutations in the gene for the c-kit tyrosine kinase receptor are strongly implicated in the developmental abnormalities of W mutant mice. To dissect further the relationship between kit and the W phenotype, retroviruses carrying the normal murine c-kit gene were constructed. In infected cells, the level of c-kit expression from these vectors varied markedly with different promoter elements, the 5' viral LTR proving to be the most effective. When introduced into cells which normally do not express c-kit, ectopic kit receptors transduced a ligand (Steel factor)-dependent proliferative signal in IL-3-dependent DA-1 myeloid cells and induced transformation in fibroblasts. Primary mutant mast cells were used to examine the effects of reconstituting functional kit expression in cells affected by W mutations. Exogenous c-kit expression rescued the defective proliferative response to Steel factor of cells from both W/Wv and W/W mutant mice. Moreover, functional kit expression also restored the capacity of W/Wv mast cells to survive and differentiate in vivo. These results imply that defective c-kit receptor function is sufficient to generate the W mutant phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Blotting, Northern
  • Genes, Viral
  • Mast Cells / metabolism*
  • Mice
  • Mutation*
  • Phenotype
  • Pigmentation / genetics
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-kit
  • RNA / genetics
  • Receptors, Cell Surface / genetics*
  • Retroviridae / genetics
  • Thymidine Kinase / genetics
  • Transfection

Substances

  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • RNA
  • Thymidine Kinase
  • Proto-Oncogene Proteins c-kit