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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
Stable URL: http://www.jstor.org/stable/38980
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Disruption of the Cbfa2 Gene Causes Necrosis and Hemorrhaging in the Central Nervous System and Blocks Definitive Hematopoiesis
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Abstract

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.

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