Castilla L H, Wijmenga C, Wang Q, Stacy T, Speck N A, Eckhaus M, Marín-Padilla M, Collins F S, Wynshaw-Boris A, Liu P P
Laboratory of Gene Transfer, National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell. 1996 Nov 15;87(4):687-96. doi: 10.1016/s0092-8674(00)81388-4.
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.
融合癌基因CBFB-MYH11由人类急性髓系白血病M4Eo亚型中的16号染色体倒位产生。通过同源重组（敲入）将部分人类MYH11 cDNA插入小鼠Cbfb基因，从而产生了携带该癌基因杂合子的小鼠胚胎干细胞（ES细胞）。嵌合小鼠无白血病，但携带敲入Cbfb-MYH11基因的ES细胞并未参与其造血组织的形成。携带Cbfb-MYH11杂合子的小鼠胚胎缺乏定型造血，并在胚胎第12.5天左右出现多处致命性出血。该表型与Cbfb或Cbfa2（AML1）纯合缺失所导致的表型非常相似，这与Cbfb-MYH11融合癌基因的显性负功能一致。然而，也观察到原始造血功能受损，提示Cbfb-MYH11可能具有额外功能。
