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, runting, morphological abnormalities, susceptibility to infections, and reductions in lymphocytes and their precursors. FACS analysis of bone marrow from mutant mice demonstrates variable reductions in pro-B and pre-B cells. While 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, respectively), normal levels are found in other individuals. In the affected mutants, some reductions are observed in many stages of B cell development. 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 can 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 development in a developmental stage-specific manner. In spite of these variable abnormalities, however, the hemopoietic system of c-abl mutant animals is surprisingly intact.
Hardin
J D
JD
Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Boast
S
S
Schwartzberg
P L
PL
Lee
G
G
Alt
F W
FW
Stall
A M
AM
Goff
S P
SP
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001853:Bone Marrow / Q000254:growth & development / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D016207:Cytokines; D016315:Proto-Oncogene Proteins c-abl