Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11
Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11
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DOI：
10.1016/s0092-8674(00)81388-4
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发表时间：
1996-11-15
期刊：
影响因子：
64.5
通讯作者：
Liu, PP
中科院分区：
文献类型：
--
作者：
Castilla, LH;Wijmenga, C;Liu, PP
融合癌基因CBFB-MYH 11由人急性髓性白血病亚型M4 Eo中的16号染色体倒位产生。通过同源重组（敲入）将人MYH 11 cDNA的一部分插入小鼠Cbfb基因中，生成该癌基因杂合的小鼠胚胎干（ES）细胞。嵌合体小鼠没有白血病，但敲入Cbfb-MYH 11基因的ES细胞对其造血组织没有贡献。Cbfb-MYH 11杂合子小鼠胚胎缺乏明确的造血功能，并在胚胎第12.5天左右发生了多个致命的胚胎。该表型与Cbfb或Cbfa 2（AML 1）纯合缺失导致的表型非常相似，与Cbfb-MYH 11融合癌基因的显性负功能一致。然而，还观察到原始造血功能受损，表明Cbfb-MYH 11可能具有其他功能。
The fusion oncogene CBFB-MYH11 is generated by a chromosome 16 inversion in human acute myeloid leukemia subtype M4Eo. Mouse embryonic stem (ES) cells heterozygous for this oncogene were generated by inserting part of the human MYH11 cDNA into the mouse Cbfb gene through homologous recombination (knock-in). Chimeric mice were leukemia free, but the ES cells with the knocked-in Cbfb-MYH11 gene did not contribute to their hematopoietic tissues. Mouse embryos heterozygous for Cbfb-MYH11 lacked definitive hematopoiesis and developed multiple fatal hemorrhages around embryonic day 12.5. This phenotype is very similar to that resulting from homozygous deletions of either Cbfb or Cbfa2 (AML1), consistent with a dominant negative function of the Cbfb-MYH11 fusion oncogene. An impairment of primitive hematopoiesis was also observed, however, suggesting a possible additional function of Cbfb-MYH11.