Inbred laboratory mice with a particular constellation of traits including defective hematopoiesis, melanogenesis (pigmentation), and gametogenesis (fertility) have been studied since the 1930s (1-3). The molecular basis for these traits was uncovered with the findings in the late 1980s that the mutationally altered genetic loci in these mice, i.e., the W (dominant white spotting) locus or the Sl (steel) locus, correspond to the genes for the cell surface tyrosine kinase type receptor c-kit and its cognate ligand, stem cell factor (SCF), respectively. Subsequently, the functional roles of the SCF/c-kit ligand/receptor pair have been intensively studied in vitro and in vivo. The receptor is expressed by and required for normal functioning of various cell types in the affected tissue systems (embryonic and adult); appropriate receptor-mediated responses require SCF, generally expressed by stromal cells in the various tissue systems (e.g., bone marrow stromal cells for hematopoiesis, skin keratinocytes for melanocyte stimulation, gonadal Sertoli cells for male germ cells, or

From: Cancer Drug Discovery and Development Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Therapeutics Edited by: G. Morstyn, M. A. Foote, and G. J. Lieschke © Humana Press Inc., Totowa, NJ

granulosa cells for female germ cells). The current state of knowledge of SCF/c-kit, particularly with respect to their role in the hematopoietic system, is reviewed in this chapter. In referencing the literature, primary citations are illustrative rather than exhaustive, and prior reviews (e.g., refs. 4-8) are cited, especially for older work.

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