The W/Wv Mouse
The hematopoietic tissues of animals and man have the capacity for extensive self-renewal, proliferation, and differentiation. Differentiation patterns of hematopoietic tissue development as outlined most recently in a review by Cline and Golde (1979) are a series of maturational steps resulting from proliferation of a pluripotent stem cell. The pluripotent stem cell, by definition, has the potential for (1) replication to identical daughter cells (which maintain this stem cell pool) and (2) extensive differentiation into committed precursors of various cell lines that make up the hematopoietic tissues (i.e., erythroid, granuloid, megakaryocyte, as well as lymphoid series) (Fig. 1). Recent work has suggested that defective hematopoietic stem cells at either the level of the pluripotent hematopoietic progenitor cell or at the committed precursor stage might result in diseases such as aplastic anemia (Hoffman et al., 1977) and Blackfan-Diamond syndrome (Hoffman et al., 1976) in man. McCulloch et al. (1964) have shown that the stem-cell defect in the anemic W/W v mouse is due to a quantitative reduction in the numbers of spleen colony-forming units (CFU; the assay for pluripotent stem cells) in the bone marrow of the W/W v mouse. In addition, the macrocytic anemia of W/W v mice (characterized by decreased red blood cell counts and hematocrit and increased mean cell volume; Table I) is considered to be an experimental model of hypoplastic anemia in man (Russell and Bernstein, 1966). The W/W v anemic mouse is an F1 mouse that is derived from the mating of two strains (the G57BL/6J mouse carrying the W v allele in the heterozygous state, and the WB/ReJ mouse carrying the W allele in the heterozygous state). Thus, when these mice are bred, F1 mice of four separate genotypes are produced, +/+, W/+, W v/+, and the W/W v anemic mouse. The +/ + mice are hematologically normal. It has been shown that the W/W v anemic mice can accept a bone marrow graft from their +/+ normal littermates and that the success of the bone marrow graft can be easily determined by testing red blood cell values in the anemic recipients (Russell et ai, 1959).
KeywordsBone Marrow Major Histocompatibility Complex Bone Marrow Cell Aplastic Anemia Bone Marrow Failure
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