[Significance of cell-to-cell interaction for migration and proliferation: an application of W and Sl mutant mice for cancer research].

A double gene dose of mutant alleles at either W or Sl locus of mice produces the pleiotropic effects of macrocytic anemia, depletion of mast cells, lack of hair pigmentation, and sterility. Although the phenotypic expression of these two mutations is very similar, underlying mechanisms are quite different. The depletion of erythrocytes, mast cells and melanocytes in W/Wv mice is attributed to a defect in their precursor cells. In fact, the transplantation of bone marrow cells from congenic +/+ mice normalizes the number of erythrocytes and mast cells in the W/Wv mice. The donor origin of erythrocytes and mast cells was confirmed by using genetic markers. In contrast, the depletion of erythrocytes, mast cells and melanocytes in the Sl/Sld mice is due to a defect of microenvironment in which precursor cells differentiate into erythrocytes, mast cells and melanocytes. Although the sterility of both W/Wv and Sl/Sld mice is attributed to the depletion of germ cells, the mechanisms of germ-cell depletion have not been clarified. Since phenotypes of W/Wv and Sl/Sld mice seem to result from defects in cell-to-cell interactions, and since cell-to-cell interactions seem to play important roles for development of cancer, the author introduced these mutant mice as tools for cancer research.