Tal1 transgenic expression reveals absence of B lymphocytes.
TAL1 oncogene encodes a helix-loop-helix transcription factor, Tal1, which is required for blood cell development, and its activation is a frequent event in T-cell acute lymphoblastic leukemia. Tal1 interacts and inhibits other helix-loop-helix factors such as E47 and HEB. To investigate the function of Tal1 in B cells, we generated Emu-TAL1 transgenic mouse line, expressing Tal1 in mouse B-cell lineage. Fluorescence-activated cell sorting (FACS) analysis of lymphocytes isolated from spleens of five out of five founders reveals complete absence of IgM- or CD19-expressing cells. Only 2% to 3% of these cells were B220+ and 100% of B220+ cells were CD43+, indicating that these mice were able to make pro-B cells. Similarly, FACS analysis of bone marrow cells in Emu-TAL1 mice revealed complete absence of B220+IgM+ and B220+CD19+ cells. Analysis of the recombination status of IgH genes revealed the presence of D-J but absence or drastic reduction of V-D-J rearrangements. Our results suggest that Tal1 overexpression in B cells results in a phenotype similar to that of B cells of E47/E2A knockout animals. This represents first in vivo evidence that Tal1 can completely inhibit E47/E2A function.
Palamarchuk
Alexey
A
Comprehensive Cancer Center, Human Cancer Genetics Program, OSU School of Medicine, Ohio State University, Columbus, Ohio 43210, USA.
Zanesi
Nicola
N
Aqeilan
Rami I
RI
Efanov
Alexey
A
Maximov
Vadim
V
Santanam
Urmila
U
Hagan
John P
JP
Croce
Carlo M
CM
Pekarsky
Yuri
Y
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D007143:Immunoglobulin Heavy Chains; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C067143:TAL1 protein, human