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Systemic Overexpression of BCL-2 in the Hematopoietic System Protects
Transgenic Mice From the Consequences of Lethal Irradiation
Jos Domen,
Kimberly L. Gandy, and
Irving L. Weissman
From the Department of Pathology and Developmental Biology, Stanford
University School of Medicine, Stanford, CA.
A new transgenic mouse has been generated in which the
proto-oncogene BCL-2 is ubiquitously overexpressed. H2K-BCL-2
transgenic mice overexpress BCL-2 in all cells of the hematolymphoid
system and have been used to assess the role of BCL-2 in protecting
cells of the hematolymphoid system from the consequences of ionizing radiation. We have expanded on previous studies that have demonstrated protection for specific (lymphoid) cell populations and show that systemic overexpression of BCL-2 can protect the hematopoietic system
as a whole, including hematopoietic stem cells (HSC), thus increasing
the radioresistance of the animal. The increase in radioresistance in
H2K-BCL-2 transgenic mice has two components: an increase in
the radioresistance of individual cells and, to a lesser extent, an
increase in the size of certain critically important cell populations,
such as HSC. Bone marrow transplantation experiments show that the
increased radioresistance of the transgenic animals is provided by
cells of the hematopoietic system. Protection against the consequences
of irradiation is not limited to the increased expression levels of
BCL-2 in transgenic mice; levels of endogenous BCL-2 are higher in
lymphocyte populations that survive irradiation in wild-type mice. We
show that ubiquitous overexpression of BCL-2 in the hematopoietic
system can be used to increase the resistance of animals to lethal
challenges such as irradiation.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2272-2282
© 1998 by The American Society of Hematology.
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