Microphthalmic mice display a B cell deficiency similar to that seen for mast and NK cells

The microphthalmic mouse (mi) possesses a 3-bp deletion of the Mi gene that alters the DNA binding site of the transcription factor gene product. This animal has diminished numbers of NK and mast cells (MC) and is osteopetrot ic due to a lack of the normal complement of functional osteoclasts, The re duction of MC has been proposed to be due to the lack of adequate c-Kit exp ression that is required for MC differentiation. However, data from other l abs has questioned this interpretation. In this report, we present data sug gesting bone marrow-derived deficiencies of the mi mouse are not due to a l ack of c-Kit expression and function, but instead due to an inhospitable en vironment within the bone marrow itself. Specifically, we have found that s uch animals also lack virtually all B cell precursors within the marrow and rely upon other lymphatic sites, such as the spleen, for B cell developmen t and maturation. Although the animal has depressed numbers of NK cells, B cells, and MC, it still possesses a normal thymus and peripheral T cells. T herefore, the block in cellular differentiation must be within the marrow e nvironment, which is essential for maturing B cells, NK cells, and MC but n ot T cells.