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Disruption of the Cbfa2 Gene Causes Necrosis and Hemorrhaging in the Central Nervous System and Blocks Definitive Hematopoiesis
Qing Wang, Terryl Stacy, Michael Binder, Miguel Marín-Padilla, Arlene H. Sharpe and Nancy A. Speck
Proceedings of the National Academy of Sciences of the United States of America
Vol. 93, No. 8 (Apr. 16, 1996), pp. 3444-3449
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/38980
Page Count: 6
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The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBFα 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption of one copy of the Cbfa2 gene significantly reduces the number of progenitors for erythroid and myeloid cells.
Proceedings of the National Academy of Sciences of the United States of America © 1996 National Academy of Sciences