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Altered lymphoid development in mice deficient for the mAF4 proto-oncogene.
1Centre d'immunologie INSERM-CNRS de Marseille Luminy, Marseille Cedex 9, France.
Blood
|July 11, 2000
Summary
Inactivating the AF4 gene in mice impaired lymphocyte development, affecting both B and T cells. This suggests AF4
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Chromosomal translocations involving the MLL gene are common in acute leukemias.
- The AF4 gene fuses with MLL in acute lymphoblastic leukemia with the t(4;11) translocation.
Purpose of the Study:
- To investigate the role of the AF4 gene in leukemogenesis and lymphocyte development.
- To understand the function of AF4 by creating a knockout mouse model.
Main Methods:
- Homologous recombination was used to inactivate the AF4 gene in mice.
- Flow cytometry was used to analyze lymphocyte populations (B and T cells) in mutant mice.
Main Results:
- AF4 mutant mice exhibited impaired development of both B and T lymphocytes.
- A significant reduction in thymic CD4/CD8 double-positive cells and altered coreceptor expression was observed.
- Impaired reconstitution of the double-positive T-cell compartment and reduced B-cell numbers in bone marrow were noted.
Conclusions:
- The AF4 gene is critical for normal lymphocyte development.
- Disruption of AF4, particularly through MLL translocations, may contribute to lymphoid leukemogenesis.
- This study provides the first functional analysis of an MLL partner gene using a knockout strategy in translocation-associated leukemias.