International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Kominami R
Niigata University

Co-Authors: Yu-ichi Wakabayashi
Institutions: Niigata University

Lymphocyte development is a complex process that involves the coordinated action of many transcription factors. We show here that a Kruppled-like factor, Bcl11b, is required in T cell development, which was isolated as a tumor suppressor gene by analyzing a region of loss of heterozygosity in thymic lymphomas. Its paralog, Bcl11a, is involved in B cell development and the two genes are associated with immune system malignancies.We have generated Bcl11b-deficient miceto elucidate roles of Bcl11b in T cell and lymphoma development. Bcl11b-/- mice showed a developmental arrest at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B or γδ T cell lineages. Their thymocytes showed unsuccessful Vβ to Dβ recombination and lacked the pre-TCR complex on the cell surface due to the lack of T cell receptor-β mRNA expression. In addition, profound apoptosis was seen in the thymus of neonatal Bcl11b-/- mice. The thymic arrest and apoptosis are the opposite of what would be predicted from the initial observation, an increase in the number of thymocytes. Therefore, Bcl11b is a key regulator of both differentiation and survival during thymocyte development and also may represent a tumor suppressor that can have positive and negative effects on cell growth.

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