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Related Experiment Videos

The mouse W/c-kit locus.

A Bernstein1, B Chabot, P Dubreuil

  • 1Division of Molecular and Developmental Biology, Mt. Sinai Hospital Research Institute, Toronto, Ontario, Canada.

Ciba Foundation Symposium
|January 1, 1990
PubMed
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The W locus mutation in mice causes developmental defects by impairing the c-kit proto-oncogene, a receptor tyrosine kinase essential for cell differentiation and haemopoiesis.

Area of Science:

  • Developmental Biology
  • Molecular Genetics
  • Hematology

Background:

  • Haemopoiesis involves extensive cell proliferation from pluripotent stem cells.
  • Understanding the molecular control of early haemopoiesis requires identifying key regulatory genes.
  • Mouse W locus mutations cause pleiotropic developmental defects, including anemia and mast cell deficiency, indicating a role in cellular differentiation.

Purpose of the Study:

  • To elucidate the molecular basis of the classical mouse W locus developmental mutation.
  • To identify and characterize genes controlling early haemopoiesis.

Main Methods:

  • Genetic linkage analysis to associate the c-kit proto-oncogene with the W locus.
  • Expression analysis of c-kit transcripts in W mutant mice.

Related Experiment Videos

  • Functional assessment of c-kit tyrosine kinase activity in mutant mast cells.
  • Analysis of c-kit gene rearrangements in W mutant alleles.

    • Main Results:

    • The c-kit proto-oncogene, encoding a receptor tyrosine kinase, is closely linked to the mouse W locus.
    • c-kit expression is observed in cell populations affected by W mutations and is influenced by these mutations.
    • Tyrosine kinase activity of c-kit is impaired in mast cells from W/Wv mutant mice.
    • Rearrangements within the c-kit gene were found in two W mutant alleles.

    Conclusions:

    • The W locus encodes the c-kit transmembrane growth factor receptor.
    • W mutations result from loss-of-function alterations affecting c-kit receptor tyrosine kinase activity.
    • This provides a molecular explanation for the haemopoietic defects in W mutant mice and highlights c-kit's role in development and haemopoiesis.