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Altered Hox expression and segmental identity in Mll-mutant mice

Nature volume 378, pages 505508 (30 November 1995) | Download Citation

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Abstract

THE mixed-lineage leukaemia gene (MLL/HRX/ALL-1) is disrupted by chromosomal translocation in human acute leukaemias that often display mixed lymphoid–myeloid phenotypes and present in infancy1–4. MLL possesses a highly conserved SET domain also found in Drosophila trithorax (trx) and Polycomb group (Pc-G) genes, which are known to regulate homeotic genes (HOM-C) in a positive or negative fashion, respectively5. Mll was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its role in pattern development. Mll heterozygous (+/−) mice had retarded growth, displayed haematopoietic abnormalities, and demonstrated bidirectional homeotic transformations of the axial skeleton as well as sternal malformations. Mll deficiency (−/−) was embryonic lethal. Anterior boundaries of Hoxa-7 and Hoxc-9 expression were shifted posteriorly in Mll +/− embryos, but their expression was abolished in Mll −/− embryos. Thus Mll is required for proper segment identity in mammals, displays haplo-insufficiency, and positively regulates Hox gene expression.

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  1. Howard Hughes Medical Institute, Division of Molecular Oncology, Departments of Medicine and Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Benjamin D. Yu
    • , Jay L. Hess
    • , Susan E. Horning
    • , Gary A. J. Brown
    •  & Stanley J. Korsmeyer

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https://doi.org/10.1038/378505a0

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