Altered Hox expression and segmental identity in Mll-mutant mice

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

Research output: Contribution to journalArticle

659 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)505-508
Number of pages4
JournalNature
Volume378
Issue number6556
StatePublished - 1995
Externally publishedYes

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Homeobox Genes
Leukemia
Embryonic Structures
Genetic Translocation
Homologous Recombination
Embryonic Stem Cells
Skeleton
Genes
Drosophila
Mammals
Phenotype
Gene Expression
Growth

ASJC Scopus subject areas

  • General

Cite this

Yu, B. D., Hess, J., Horning, S. E., Brown, G. A. J., & Korsmeyer, S. J. (1995). Altered Hox expression and segmental identity in Mll-mutant mice. Nature, 378(6556), 505-508.

Altered Hox expression and segmental identity in Mll-mutant mice. / Yu, Benjamin D.; Hess, Jay; Horning, Susan E.; Brown, Gary A J; Korsmeyer, Stanley J.

In: Nature, Vol. 378, No. 6556, 1995, p. 505-508.

Research output: Contribution to journalArticle

Yu, BD, Hess, J, Horning, SE, Brown, GAJ & Korsmeyer, SJ 1995, 'Altered Hox expression and segmental identity in Mll-mutant mice', Nature, vol. 378, no. 6556, pp. 505-508.
Yu BD, Hess J, Horning SE, Brown GAJ, Korsmeyer SJ. Altered Hox expression and segmental identity in Mll-mutant mice. Nature. 1995;378(6556):505-508.
Yu, Benjamin D. ; Hess, Jay ; Horning, Susan E. ; Brown, Gary A J ; Korsmeyer, Stanley J. / Altered Hox expression and segmental identity in Mll-mutant mice. In: Nature. 1995 ; Vol. 378, No. 6556. pp. 505-508.
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