Animal Models Of Hematopoietic Growth Factor Deficiency

Early models of induced factor deficiency relied on immunologic mechanisms to neutralize factor activity. The ability to disrupt individual genes selectively by gene targeting provided a powerful method of generating mice with deficiencies of either selected ligands, receptors, or downstream-signaling molecules. Such engineered deficiencies have usually been designed to be absolute and are life-long, providing insight into the cumulative effects of nonredundant roles of the absent gene product. This genetic approach has been pre-eminent in defining the essential physiologic role of various factors. However, animal models with less-than-total factor deficiency have been generated using other methodologies, both before the gene targeting era and more recently. These models offer several advantages: although they may not result in absolute factor deficiency, they offer flexibilities including inducibility, reversibility, and nonlethality. A new approach, not yet applied to studying HGF, is the use of RNA interference (1). Various experimental approaches to factor ablation are listed in Table 1 with some comparative relative advantages and disadvantages.

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