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 Blood, 1 January 2008, Vol. 111, No. 1, pp. 160-164.
Prepublished online as a Blood First Edition Paper on September 13, 2007; DOI 10.1182/blood-2007-07-099754.

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HEMATOPOIESIS

Brief Report

Simultaneous loss of β- and {gamma}-catenin does not perturb hematopoiesis or lymphopoiesis

Ute Koch1, Anne Wilson2, Monica Cobas2, Rolf Kemler3, H. Robson MacDonald2, and Freddy Radtke1

1 Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Epalinges, Switzerland; 2 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; and 3 Department of Molecular Embryology, Max-Planck Institute of Immunology, Freiburg, Germany

Hematopietic stem cells (HSCs) maintain life-long hematopoiesis in the bone marrow via their ability to self-renew and to differentiate into all blood lineages. Although a central role for the canonical wnt signaling pathway has been suggested in HSC self-renewal as well as in the development of B and T cells, conditional deletion of β-catenin (which is considered to be essential for Wnt signaling) has no effect on hematopoiesis or lymphopoiesis. Here, we address whether this discrepancy can be explained by a redundant and compensatory function of {gamma}-catenin, a close homolog of β-catenin. Unexpectedly, we find that combined deficiency of β- and {gamma}-catenin in hematopoietic progenitors does not impair their ability to self-renew and to reconstitute all myeloid, erythroid, and lymphoid lineages, even in competitive mixed chimeras and serial transplantations. These results exclude an essential role for canonical Wnt signaling (as mediated by β- and/or {gamma}-catenin) during hematopoiesis and lymphopoiesis.


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