Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis

Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis
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DOI:
10.1073/pnas.93.8.3444
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发表时间:
1996-04-16
影响因子:
11.1
通讯作者:
Speck, NA
Speck, NA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang, Q;Stacy, T;Speck, NA

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CBFA 2(AML 1)基因编码异二聚体核心结合因子的DNA结合亚基。CBFA 2基因被(8;21)、(3;21)和(12; 21)与人类白血病和骨髓增生异常相关的染色体易位,缺乏能够结合DNA的CBF α 2蛋白的小鼠在胚胎11.5和12.5天之间由于中枢神经系统(CNS)的衰老而死亡,在颅神经和脊神经的神经/CNS界面处,以及在沿着假定脊髓的体节/体节间区域中,出血之前是这些区域中的对称的双侧坏死,在Cbfa 2缺陷型胚胎中不发生促红细胞生成和骨髓生成,并且Cbfa 2基因的一个拷贝的破坏显著减少了红系和髓系细胞的祖细胞的数量。
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.