The proto-oncogene c-abl encodes a tyrosine kinase that is hypothesize
d to function in proliferation-stimulatory signaling pathways. Previou
s work on mice homozygous for targeted mutations in the c-abl gene (ab
l(m1) and abl(2) mutant strains) has demonstrated multiple defects, in
cluding a susceptibility to infections that results in a high mortalit
y rate after weaning. FAGS analysis of the hemopoietic system of c-abl
mutants demonstrated variable reductions in B and T lymphocytes in ad
ult bone marrow, thymus, spleen, and peripheral blood, In addition, bo
ne marrow from mutants showed a decreased ability to respond to interl
eukin-7. We further found that B cells from abl(ml) mice had a reduced
ability to respond to lipopolysaccharide (decreased to 10% of control
response) that was dependent on the culture conditions and the tissue
of origin of B cells. Peripheral blood from the mutants also had a re
duced response to the T cell mitogen concanavalin A, Immune response i
n abl(m1) mice as determined by the mixed lymphocyte response and the
sheep red blood cell plaque-forming assay was grossly normal. These fi
ndings suggest that although specific signaling pathways in lymphocyte
s may involve c-Abl, the immune system can function in the absence of
a normal c-abl gene product. (C) 1996 Academic Press, Inc.