BONE-MARROW B-LYMPHOCYTE DEVELOPMENT IN C-ABL-DEFICIENT MICE

Mice homozygous for a mutation in the c-abl tyrosine kinase gene have multiple defects including high postnatal mortality, ranting, morpholo gical abnormalities, susceptibility to infections, and reductions in l ymphocytes and their precursors. FAGS analysis of bone marrow from mut ant mice demonstrates variable reductions ire pro-E and pre-B cells. W hile the numbers of cells in these populations are profoundly reduced in some mutants (16 and 1.2% of control pro-B and pre-B cells, respect ively), normal levels are found in other individuals. In the affected mutants, some reductions are observed in many stages of B cell develop ment. The response of B cell precursors to the cytokine interleukin-7 is variably affected while that of several other cytokines (stem cell factor, interleukin-3, GM-CSF, G-CSF, and erythropoietin) is normal in c-abl mutants. The population defects caused by the c-abl mutation ca n be recreated in normal mice by the transfer of adult bone marrow but , surprisingly, not fetal liver. These studies demonstrate that c-Abl signaling pathways may play a role in the earliest stages of B cell de velopment in a developmental stage-specific manner. In spite of these variable abnormalities, however, the hemopoietic system of c-abl mutan t animals is surprisingly intact. (C) 1995 Academic Press, Inc.