Mast cells have long been known to play a detrimental role in the pathogenesis 
of IgE-associated allergic disorders by their ability to release a wide variety 
of pro-inflammatory mediators. A number of studies, however, have demonstrated 
that mast cells play a beneficial role in innate host defense against bacterial 
infections. Since mast cells clearly play both physiological and 
pathophysiological functions in the body, it is important to learn about the 
components of mast cells that drive these responses. The functional roles of 
mast cell in vivo have been principally characterized by comparing the 
biological responses in mast cell-deficient mice (WBB6F(1)-W/W(v)), their normal 
wild-type littermates (WBB6F(1)-+/+) and mast cell deficient mice reconstituted 
locally or systemically with mast cells cultured from the bone marrow cells of 
WBB6F(1)-+/+ mice (WBB6F(1)-W/W(v)+MC). Recently investigators have demonstrated 
that mast cell-deficient mice (WBB6F(1)-W/W(v)) can be reconstituted with mast 
cells derived in vitro from the bone marrow cells of certain gene knock-out mice 
or genetically-manipulated embryonic stem cells. This novel approach of 
analyzing the biological consequences of gene mutations in mast cells will help 
us to better understand the role of individual gene products in mast cell 
responses. In this review, we discuss these new approaches to investigate the 
functions of mast cells in vivo.