title: Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.
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.
authors.affiliation: Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Stacy
authors.forename: M
authors.initials: M
authors.lastname: Binder
authors.forename: M
authors.initials: M
authors.lastname: Marin-Padilla
authors.forename: A H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: N A
authors.initials: NA
authors.lastname: Speck
mesh_terms: D000818:Animals; D001483:Base Sequence; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics; D018390:Gene Targeting; D006410:Hematopoiesis / Q000235:genetics*; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D009336:Necrosis; D009363:Neoplasm Proteins / Q000235:genetics*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors