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 CBF alpha 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Central Nervous System Diseases / genetics*
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Central Nervous System Diseases / pathology
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Core Binding Factor Alpha 2 Subunit
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DNA Primers / genetics
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DNA, Complementary / genetics
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DNA-Binding Proteins*
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Erythropoiesis / genetics
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Female
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Fetal Death / genetics
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Gene Targeting
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Hematopoiesis / genetics*
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Hemorrhage / genetics
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Molecular Sequence Data
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Mutation
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Necrosis
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Neoplasm Proteins / genetics*
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Pregnancy
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Proto-Oncogene Proteins*
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Proto-Oncogenes*
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Transcription Factors / genetics*
Substances
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Core Binding Factor Alpha 2 Subunit
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DNA Primers
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DNA, Complementary
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DNA-Binding Proteins
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Neoplasm Proteins
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Proto-Oncogene Proteins
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RUNX1 protein, human
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Runx1 protein, mouse
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Transcription Factors