ABSTRACT
In the mouse two mutations that result in severe macrocytic anemia, the dominant white spotting (W) locus on chromosome 5 and the Steel (Sl) locus on chromosome 10, have provided unique biological insights into hematopoiesis and the important role of the cellular microenvironment in this process. This chapter reviews and discusses the information that has emerged from the analysis of the molecular basis of these two loci. The molecular analysis of the W and Sl loci has also led to the isolation of a novel and potent hematopoietic growth, survival, and/or adhesion factor that may have interesting therapeutic applications in treatment of certain anemias and other disorders. Mouse strains carrying mutations at either dominant W or Sl locus have been particularly useful in understanding the molecular mechanisms that regulate hematopoiesis. Both W and Sl mutant mice have abnormal development of hematopoietic stem cells as well as deficits in erythroid and mast cells, primordial germ cells, and neural crest-derived melanoblasts.
