Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation.
Blood
; 100(2): 491-500, 2002 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-12091340
ABSTRACT
The tal-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor required for primitive and definitive hematopoiesis. Additionally, ectopic activation of the tal-1 gene during T lymphopoiesis occurs in numerous cases of human T-cell acute lymphoblastic leukemia. With the use of transgenic mice, we show that, in adult hematopoiesis, constitutive expression of TAL-1 protein causes disorders in the hematopoietic lineages that normally switch off tal-1 gene expression during their differentiation process. Myelopoiesis was characterized by a moderate increase of myeloid precursors and by Sca-1 antigen persistence. Although no lymphoid leukemia was observed, T lymphopoiesis and B lymphopoiesis were severely impaired. Transgenic mice showed reduced thymic cellularity together with a decrease in double-positive cells and a concurrent increase in the single-positive population. B cells exhibited a differentiation defect characterized by a reduction of the B-cell compartment most likely because of a differentiation block upstream of the intermediate pro-B progenitor. B cells escaping this defect developed normally, but transgenic splenocytes presented a defect in immunoglobulin class switch recombination. Altogether, these results enlighten the fine-tuning of TAL-1 expression during adult hematopoiesis and indicate why TAL-1 expression has to be switched off in the lymphoid lineages.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Linfócitos B
/
Linfócitos T
/
Antígenos Ly
/
Proteínas Proto-Oncogênicas
/
Proteínas de Ligação a DNA
/
Proteínas de Membrana
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article