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Altered Hox expression and segmental identity in Mll-mutant mice

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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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Authors and Affiliations

  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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  1. Benjamin D. Yu
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  2. Jay L. Hess
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  3. Susan E. Horning
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  4. Gary A. J. Brown
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Yu, B., Hess, J., Horning, S. et al. Altered Hox expression and segmental identity in Mll-mutant mice. Nature 378, 505–508 (1995). https://doi.org/10.1038/378505a0

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