POSTERIOR TRANSFORMATION, NEUROLOGICAL ABNORMALITIES, AND SEVERE HEMATOPOIETIC DEFECTS IN MICE WITH A TARGETED DELETION OF THE BMI-1 PROTOONCOGENE
POSTERIOR TRANSFORMATION, NEUROLOGICAL ABNORMALITIES, AND SEVERE HEMATOPOIETIC DEFECTS IN MICE WITH A TARGETED DELETION OF THE BMI-1 PROTOONCOGENE
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DOI：
10.1101/gad.8.7.757
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发表时间：
1994-04-01
影响因子：
10.5
通讯作者：
BERNS, A
中科院分区：
文献类型：
--
作者：
VANDERLUGT, NMT;DOMEN, J;BERNS, A
bmi-1 原癌基因与 E mu-myc 转基因小鼠的 B 细胞淋巴瘤发生有关。 Bmi-1 蛋白的独特结构域在果蝇蛋白后性梳中高度保守，后性梳是多梳组的成员，参与在发育过程中维持同源异型基因的稳定抑制。我们通过 ES 细胞中的同源重组灭活了小鼠种系中的 bmi-1 基因。无效突变小鼠表现出三种表型改变：（1）造血细胞数量逐渐减少，这些细胞对有丝分裂原的增殖反应受损； (2) 神经系统异常，表现为步态共济失调和偶发性癫痫发作； (3)后向变换，大多数情况下沿着骨骼的完整前后轴。观察结果表明，Bmi-1 在胚胎发育过程中的形态发生以及整个产前和产后的造血过程中发挥着重要作用。此外，这些数据提供了哺乳动物多梳族同源物功能保守的第一个证据。
The bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells. Null mutant mice display three phenotypic alterations: (1) a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens; (2) neurological abnormalities manifested by an ataxic gait and sporadic seizures; (3) posterior transformation, in most cases along the complete anteroposterior axis of the skeleton. The observations indicate that Bmi-1 plays an important role in morphogenesis during embryonic development and in hematopoiesis throughout pre- and postnatal life. Furthermore, these data provide the first evidence of functional conservation of a mammalian Polycomb group homolog.